Mitochondrial Division and Fusion
Mitochondria are highly dynamic organelles that continually grow, divide, and fuse in tightly regulated ways. These dynamic behaviors are essential for maintaining mitochondrial health, enabling damaged mitochondria to be separated by division and healthy mitochondria to exchange contents through fusion. Our laboratory studies the molecular and cellular mechanisms that govern mitochondrial fusion and division and how their balance shapes mitochondrial structure and function.
Through pioneering work combining yeast genetics, mitochondrial biochemistry, and advanced microscopy in the late 1990s, we discovered fundamental principles underlying mitochondrial dynamics. We identified and characterized conserved regulators of fusion and division, including dynamin-related GTPases such as Opa1, Mfn1, Mfn2, and Drp1, as well as a mitochondrial quality-control pathway mediated by Parkin, Pink1, and Oma1.
To connect basic discovery with human health, we translate these findings into mammalian systems using genetically engineered mouse models and precise genome editing approaches. Our research integrates biochemical reconstitution, state-of-the-art imaging, and multi-omics analyses to understand how mitochondrial structure influences energy metabolism, mitophagy, and innate immune responses. By studying these processes in models of neurodegeneration, metabolic disease, heart failure, and cancer, our work aims to uncover fundamental mechanisms of mitochondrial regulation and identify new strategies for therapeutic intervention.
Complete List of Published Work
https://pubmed.ncbi.nlm.nih.gov/?term=sesaki%20h&sort=pubdate&size=20&pos=2
Selected Publications
Yamada T, Ikeda A, Murata D, Wang H, Zhang C, Khare P, Adachi Y, Ito F, Quirós PM, Blackshaw S, López-Otín C, Langer T, Chan DC, Le A, Dawson VL, Dawson TM, Iijima M, Sesaki H. (2025) Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1. Nature. 639:776-78
Adachi Y, Torres M, Hunter AH, Cho WJ, Pan M, Han X, Du G, Qi L, Iijima M, Sesaki H. (2025). AGPAT2 acts at the crossroads of lipid biosynthesis and DRP1-mediated ER morphogenesis. Nat Commun. 16:11473.
Murata D, Ito F, Tang G, Iwata W, Yeung N, West JJ, Ewald AJ, Wang X, Iijima M, Sesaki H. (2024). mCAUSE: Prioritizing mitochondrial targets that alleviate pancreatic cancer cell phenotypes. iScience. 27:1 10880
Murata D, Roy S, Lutsenko S, Iijima M, Sesaki H. (2024). Slc25a3-dependent copper transport controls flickering-induced Opa1 processing for mitochondrial safeguard. Dev Cell. 59: 2578-259
Ikeda A, Iijima M, Sesaki H. (2024). Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior. iScience. 27: 109874.
Prashar A, Bussi C, Fearns A, Capurro MI, Gao X, Sesaki H, Gutierrez MG, Jones NL. (2024). Lysosomes drive the piecemeal removal of mitochondrial inner membrane. Nature. 632: 1110-1117.
Yeung N, Murata D, Iijima M, Sesaki H. (2023). Role of human HSPE1 for OPA1 processing independent of HSPD1. iScience. 26: 106067.
Baixauli F, Piletic K, Puleston DJ, Villa M, Field CS, Flachsmann LJ, Quintana A, Rana N, Edwards-Hicks J, Matsushita M, Stanczak M, Grzes KM, Kabat AM, Fabri M, Caputa G, Kelly B, Corrado M, Musa Y, Duda KJ, Mittler G, O’Sullivan D, Sesaki H, Jenuwein T, Buescher JM, Pearce EJ, Sanin DE, Pearce EL. (2022). An LKB1-mitochondria axis controls Th17 effector function. Nature. 610: 555-561.
Murata D, Yamada T, Tokuyama T, Arai K, Quirós PM, López-Otín C, Iijima M, Sesaki H. (2020). Mitochondrial safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation. EMBO J. 39: e105074.
Yamada T, Murata D, Kleiner DE, Anders R, Rosenberg AZ, Kaplan J, Hamilton JP, Aghajan M, Levi M, Wang NY, Dawson TM, Yanagawa T, Powers AF, Iijima M, Sesaki H. (2020). Prevention and regression of megamitochondria and steatosis by blocking mitochondrial fusion in the liver. iScience. 25: 103996.
Zhou Z, Torres M, H Sha, Halbrook CJ., Van den Bergh F, Reinert RB, Yamada T, Wang S, Luo Y, Hunter A, Wang C, Sanderson TH, Liu M, Taylor A, Sesaki H, Lyssiotis CA, Wu J, Kersten S, Beard D, Qi L. (2020). Regulation of endoplasmic reticulum-mitochondria contacts and mitochondrial dynamics by Sel1L-Hrd1 ERAD during thermogenesis. Science. 368: 54-60.
Adachi Y, Kato T, Yamada T, Murata D, Arai K, Stahelin RV, Chan DC, Iijima M, Sesaki H. (2019). Drp1 Tubulates the ER in a GTPase-Independent Manner. Mol Cell. 80: 621-632.
Itoh K, Murata D, Kato T, Yamada T, Araki Y, Saito A, Adachi Y, Igarashi A, Li S, Pletnikov M, Huganir RL, Watanabe S, Kamiya A, Iijima M, Sesaki H. (2019). Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division. Elife. 8. pii: e44739.
Yamada T, Dawson TM, Yanagawa T, Iijima M, Sesaki H. (2019). SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 15: 2012-2018.
Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A, Kato T, Araki Y, Huganir RL, Dawson TM, Yanagawa T, Okamoto K, Iijima M, Sesaki H. (2018). Mitochondrial stasis reveals p62-mediated ubiquitination in parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 28: 588-604
Buck MD, O’Sullivan D, Klein Geltink RI, Curtis JD, Chang CH, Sanin DE, Qiu J, Kretz O, Braas D, van der Windt GJ, Chen Q, Huang SC, O’Neill CM, Edelson BT, Pearce EJ, Sesaki H, Huber TB, Rambold AS, Pearce EL. (2016). Mitochondrial dynamics controls T cell fate through metabolic programming. Cell. 166: 63-76
Adachi Y, Itoh K, Yamada T, Cerveny KL, Suzuki TL, Macdonald P, Frohman MA, Ramachandran R, Iijima M, Sesaki H. (2016). Coincident phosphatidic acid interaction restrains Drp1 in mitochondrial division. Mol Cell. 63: 1034-43
Kageyama Y, Hoshijima M, Seo K, Bedja D, Sysa-Shah P, Andrabi S, Chen W, Höke A, Dawson VL, Dawson TM, Gabrielson K, Kass DA, Iijima M, Sesaki H. (2014). Parkin- independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain. EMBO J. 33: 2798-2813.
Kageyama Y, Zhang Z, Roda R, Fukaya M, Wakabayashi J, Wakabayashi N, Kensler TW, Reddy PH, Iijima M, Sesaki H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol. 197: 535-51.
Tamura Y, Itoh K, Sesaki H. SnapShot: Mitochondrial dynamics. Cell. 2011;145:1158-11581e.
Tamura Y, Iijima M, Sesaki H. (2010). Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation. EMBO J. 29: 2875-2887.
Tamura Y, Endo T, Iijima M, Sesaki H. (2009). Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. J Cell Biol. 185: 1029-1045.
Wakabayashi J, Zhang Z, Wakabayashi N, Tamura Y, Fukaya M, Kensler TW, Iijima M, Sesaki H. (2009). The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol. 186: 805-816.
Cerveny KL, Studer SL, Jensen RE, Sesaki H. (2007). Yeast mitochondrial division and distribution requires the cortical Num1 protein. Dev Cell. 12:363-375.
Sesaki H, Dunn CD, Iijima M, Shepard KA, Yaffe MP, Machamer CE, Jensen RE. (2006). Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of Mgm1p. J Cell Biol. 173: 651-658.
Sesaki H, Jensen RE. (2001). UGO1 encodes an outer membrane protein required for mitochondrial fusion. J Cell Biol. 152: 1123-34.
Sesaki H, Jensen RE. (1999) Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J Cell Biol. 147: 699-706.
Publications
Yamada T, Ikeda A, Murata D, Wang H, Zhang C, Khare P, Adachi Y, Ito F, Quirós PM, Blackshaw S, López-Otín C, Langer T, Chan DC, Le A, Dawson VL, Dawson TM, Iijima M, Sesaki H. (2025) Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1. Nature. 639:776-78
Adachi Y, Torres M, Hunter AH, Cho WJ, Pan M, Han X, Du G, Qi L, Iijima M, Sesaki H. (2025). AGPAT2 acts at the crossroads of lipid biosynthesis and DRP1-mediated ER morphogenesis. Nat Commun. 16:11473.
Senoo H, Wai M, Matsubayashi HT, Sesaki H, Iijima M. Hetero-oligomerization of Rho and Ras GTPases Connects GPCR Activation to mTORC2-AKT Signaling. Cell Rep. 2020 Nov 24;33(8):108427
Adachi Y, Kato T, Yamada T, Murata D, Arai K, Stahelin RV, Chan DC, Iijima M, Sesaki H. Drp1 Tubulates the ER in a GTPase-Independent Manner. Mol Cell. 2020 Nov 19;80(4):621-632
Murata D, Yamada T, Tokuyama T, Arai K, Quirós PM, López-Otín C, Iijima M, Sesaki H. Mitochondrial Safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation. EMBO J. 2020 Nov 17;39(24):e105074
Kato T, Yamada T, Nakamura H, Igarashi A, Anders RA, Sesaki H, Iijima M. The Loss of Nuclear PTEN Increases Tumorigenesis in a Preclinical Mouse Model for Hepatocellular Carcinoma. iScience. 2020 Sep 10;23(10):101548
Yanagi T, Kitamura S, Imafuku K, Suto A, Maeda T, Tanaka S, Sesaki H, Abe R, Shimizu H. Loss of dynamin-related protein 1 (Drp1) does not affect epidermal development or UVB-induced apoptosis but does accelerate UVB-induced carcinogenesis. J Dermatol Sci. 2020 Aug;99(2):109-118.
Forrester SJ, Preston KJ, Cooper HA, Boyer MJ, Escoto KM, Poltronetti AJ, Elliott KJ, Kuroda R, Miyao M, Sesaki H, Akiyama T, Kimura Y, Rizzo V, Scalia R, Eguchi S. Mitochondrial Fission Mediates Endothelial Inflammation. Hypertension. 2020 Jul;76(1):267-276.
Li X, Yang L, Mao Z, Pan X, Zhao Y, Gu X, Eckel-Mahan K, Zuo Z, Tong Q, Hartig SM, Cheng X, Du G, Moore DD, Bellen HJ, Sesaki H, Sun K. Novel role of dynamin-related-protein 1 in dynamics of ER-lipid droplets in adipose tissue. FASEB J. 2020 Jun;34(6):8265-8282
Raynor J, Liu C, Dhungana Y, Guy C, Chapman N, Shi H, Neale G, Sesaki H, Chi H. Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions. J Exp Med. 2020. In press.
Zhou Z, Torres M, H Sha, Halbrook CJ., Van den Bergh F, Reinert RB, Yamada T, Wang S, Luo Y, Hunter A, Wang C, Sanderson TH, Liu M, Taylor A, Sesaki H, Lyssiotis CA, Wu J, Kersten S, Beard D, Qi L. Regulation of endoplasmic reticulum-mitochondria contacts and mitochondrial dynamics by Sel1L-Hrd1 ERAD during thermogenesis. Science. 2020. In press.
Murata D, Arai K, Iijima M, Sesaki H. Mitochondrial Division, Fusion and Degradation. J Biochem. 2020;167:233-241
Hinge A, He J, Bartram J, Javier J, Xu J, Fjellman E, Sesaki H, Li T, Yu J, Wunderlich M, Mulloy J, Kofron M, Salomonis N, Grimes HL, Filippi MD. Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition. Cell Stem Cell. 2020 Mar 5;26(3):420-430
Wang Y, An H, Liu T, Qin C, Sesaki H, Guo S, Radovick S, Hussain M, Maheshwari A, Wondisford FE, O'Rourke B, He L. Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK. Cell Rep. 2019 Nov 5;29(6):1511-1523.
Itoh K, Murata D, Kato T, Yamada T, Araki Y, Saito A, Adachi Y, Igarashi A, Li S, Pletnikov M, Huganir RL, Watanabe S, Kamiya A, Iijima M, Sesaki H. Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division. Elife. 2019 Oct 11;8. pii: e44739.
Sarbajeet Nagdas, Jennifer A. Kashatus, Aldo Nascimento, Riley E. Trainor, Sarah R. Pollock, Sara J. Adair, Alex D. Michaels, Hiromi Sesaki, Edward B. Stelow, Todd W. Bauer and David F. Kashatus. Drp1 promotes KRas-driven metabolic changes to drive pancreatic tumor growth. Cell Reports. In press
Michael P. Catanzaro, Ashley Weiner, Amanda Kaminaris, Fei Cai, Cairong Li, Fengyi Zhao, Satoru Kobayashi, Tamayo Kobayashi, Yuan Huang, Hiromi Sesaki, Qiangrong Liang. Doxorubicin-induced Cardiomyocyte Death is Mediated by Unchecked Mitochondrial Fission and Mitophagy. FASEB J. In press.
Yamada T, Dawson TM, Yanagawa T, Iijima M, Sesaki H. SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 2019; In press.
Senoo H, Kamimura K, Kimura R, Nakajima A, Sawai S, Sesaki H, Iijima M. Phosphorylated Rho-GDP directly activates mTORC2 Kinase toward AKT through dimerization with Ras-GTP to regulate cell migration. Nature Cell Biology. 2019; Epub ahead of Print
Palma E, Ma X, Riva A, Iansante V, Dhawan A, Wang S, Ni HM, Sesaki H, Williams R, Ding WX, Chokshi S. Dynamin-1-Like Protein Inhibition Drives Megamitochondria Formation as an Adaptive Response in Alcohol-Induced Hepatotoxicity. Am J Pathol. 2019 Mar;189(3):580-589.
Kojima R, Kakimoto Y, Furuta S, Itoh K, Sesaki H, Endo T, Tamura Y. Maintenance of Cardiolipin and Crista Structure Requires Cooperative Functions of Mitochondrial Dynamics and Phospholipid Transport. Cell Rep. 2019 Jan 15;26(3):518-528.
Genin EC, Bannwarth S, Lespinasse F, Ortega-Vila B, Fragaki K, Itoh K, Villa E, Lacas-Gervais S, Jokela M, Auranen M, Ylikallio E, Mauri-Crouzet A, Tyynismaa H, Vihola A, Aug G, Cochaud C, Sesaki H, Ricci JE, Udd B, Vives-Bauza C, Paquis-Flucklinger V. Loss of MICOS complex integrity and mitochondrial damage, but not TDP-43 mitochondrial localisation, are likely associated with severity of CHCHD10-related diseases. Neurobiol Dis. 2018 Nov;119:159-171.
Adachi Y, Iijima M, Sesaki H. An unstructured loop that is critical for interactions of the stalk domain of Drp1 with saturated phosphatidic acid. Small GTPases. 2018 Nov 2;9(6):472-479. doi: 10.1080/21541248.2017.1321614. Epub 2017 Jun 23.
Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A, Kato T, Araki Y, Huganir RL, Dawson TM, Yanagawa T, Okamoto K, Iijima M and Sesaki H. (2018). Mitochondrial stasis reveals p62-mediated ubiquitination in parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 2018 Oct 2;28(4):588-604.e5.
Riley JS, Quarato G, Cloix C, Lopez J, O'Prey J, Pearson M, Chapman J, Sesaki H, Carlin LM, Passos JF, Wheeler AP, Oberst A, Ryan KM, Tait SW. Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis. EMBO J. 2018 Sep 3;37(17). pii: e99238.
Hennings TG, Chopra DG, DeLeon ER, VanDeusen HR, Sesaki H, Merrins MJ, Ku GM. In Vivo Deletion of Beta-Cell Drp1 Impairs Insulin Secretion Without Affecting Islet Oxygen Consumption. Endocrinology. 2018 Sep 1;159(9):3245-3256.
Itoh K, Adachi Y, Yamada T, Suzuki TL, Otomo T, McBride HM, Yoshimori T, Iijima M, Sesaki H. A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane. J Biol Chem. 2018 Jul 27;293(30):11809-11822.
Igarashi, A., Itoh, K., Yamada, T., Adachi, Y., kato, T., Murata, D., Sesaki, H., and Iijima, M. (2018). Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility. J Biol Chem. 2018 Jun 15;293(24):9292-9300
Kwon D, Sesaki H, Kang SJ. 2018. Intracellular calcium is a rheostat for the STING signaling pathway. Biochem Biophys Res Commun. 2018 Jun 2;500(2):497-503.
Nemani N, Carvalho E, Tomar D, Dong Z, Ketschek A, Breves SL, Jaña F, Worth AM, Heffler J, Palaniappan P, Tripathi A, Subbiah R, Riitano MF, Seelam A, Manfred T, Itoh K, Meng S, Sesaki H, Craigen WJ, Rajan S, Shanmughapriya S, Caplan J, Prosser BL, Gill DL, Stathopulos PB, Gallo G, Chan DC, Mishra P, Madesh M. 2018. MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. Cell Rep. 2018 Apr 24;23(4):1005-1019.
Jouroukhin Y, Kageyama Y, Misheneva V, Shevelkin A, Andrabi S, Prandovszky E, Yolken RH, Dawson VL, Dawson TM, Aja S, Sesaki H, Pletnikov MV. 2018. DISC1 regulates lactate metabolism in astrocytes: implications for psychiatric disorders. Transl Psychiatry. 2018 Apr 12;8(1):76. doi: 10.1038/s41398-018-0123-9.
Roy S, Esmaeilniakooshkghazi A, Patnaik S, Wang Y, George SP, Ahrorov A, Hou JK, Herron AJ, Sesaki H, Khurana S. 2018. Villin-1 and Gelsolin Regulate Changes in Actin Dynamics That Affect Cell Survival Signaling Pathways and Intestinal Inflammation Gastroenterology. 2018 Apr;154(5):1405-1420
Gajendiran P, Vega LI, Itoh K, Sesaki H, Vakili MR, Lavasanifar A, Hong K, Mezey E, Ganapathy-Kanniappan S. 2018. Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin. J Cell Mol Med. 2018 Apr;22(4):2210-2219. doi: 10.1111/jcmm.13501. Epub 2018 Feb 4.
Perry HM, Huang L, Wilson RJ, Bajwa A, Sesaki H, Yan Z, Rosin DL, Kashatus DF, Okusa MD. 2018. Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI. J Am Soc Nephrol. 2018 Jan;29(1):194-206
Kameoka S, Adachi Y, Okamoto K, Iijima M, Sesaki H. 2017. Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics. Trends Cell Biol. [Epub ahead of print].
Gerber S, Charif M, Chevrollier A, Chaumette T, Angebault C, Kane MS, Paris A, Alban J, Quiles M, Delettre C, Bonneau D, Procaccio V, Amati-Bonneau P, Reynier P, Leruez S, Calmon R, Boddaert N, Funalot B, Rio M, Bouccara D, Meunier I, Sesaki H, Kaplan J, Hamel CP, Rozet JM, Lenaers G. 2017. Mutations in DNM1L, as in OPA1, result indominant optic atrophy despite opposite effectson mitochondrial fusion and fission. Brain. 140(10):2586-2596.
Santoro A, Campolo M, Liu C, Sesaki H, Meli R, Liu ZW, Kim JD, Diano S. 2017. DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons. Cell Metab. 25(3):647-660.
Adachi Y, Itoh K, Iijima M, Sesaki H. 2017. Assay to measure interactions between purified Drp1 and synthetic liposomes. Bio-Protocol. Vol 7, Iss 9.
Bordt EA, Clerc P, Roelofs BA, Saladino AJ, Tretter L, Adam-Vizi V, Cherok E, Khalil A, Yadava N, Ge SX, Francis TC, Kennedy NW, Picton LK, Kumar T, Uppuluri S, Miller AM, Itoh K, Karbowski M, Sesaki H, Hill RB, Polster BM. 2017. The putative Drp1 inhibitor mdivi-1 Is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species. Dev Cell. 2017;40(6):583-594.
Pereira R, Tadinada SM, Zasadny FM, Oliveira K, Pires KM, Olvera A, Jeffers J, Souvenir R, Mcglauflin R, Seei A, Funari T, Sesaki H, Potthoff MJ, Adams CM, Anderson EJ, Abel ED. 2017. OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance. EMBO J. 2017 Jun 12. pii: e201696179. doi: 10.15252/embj.201696179. [Epub ahead of print]
Cho B, Cho HM, Jo MY, Kim HD, Song M, Moon C, Kim H, Kim K,
Sesaki H, Rhyu IJ, Kim H. Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division.
Nat Commun. 2017 Jun 9;8:15754. doi: 10.1038/ncomms15754.
Yamada T, Adachi Y, Yanagawa T, Iijima M, Sesaki H. 2017. p62/sequestosome-1 knockout delays neurodegeneration induced by Drp1 loss. Neurochem Int. 2017 May 18. pii: S0197-0186(17)30189-4. doi: 10.1016/j.neuint.2017.05.012.
Rohani A, Moore JH, Kashatus JA, Sesaki H, Kashatus DF, Swami NS. Label-Free Quantification of Intracellular Mitochondrial Dynamics Using Dielectrophoresis. Anal Chem. 2017 Jun 6;89(11):5757-5764. doi: 10.1021/acs.analchem.6b04666. Epub 2017 May 15
Rogers MA, Maldonado N, Hutcheson JD, Goettsch C, Goto S, Yamada I, Faits T, Sesaki H, Aikawa M, Aikawa E. 2017. Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress. Circ Res. 121(3):220-233.
Yang J-M, Schiapparelli P, Nguyen H-N, Igarashi A, Zhang Q, Abbadi S, Amzel LM, Sesaki H, Quinones-Hinojosa A and Iijima M. 2017. Characterization of PTEN mutations in brain cancer reveals that PTEN mono-ubiquitination promotes protein stability and nuclear localization. Oncogene. Jun 29;36(26):3673-3685. doi: 10.1038/onc.2016.493. Epub 2017 Mar 6.
Yang X, Wang H, Ni HM, Xiong A, Wang Z, Sesaki H, Ding WX, Yang L. 2017. Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in mice. Redox Biol. 12:264-273
Salka K, Bhuvanendran S, Wilson K, Bozidis P, Mehta M, Rainey K, Sesaki H, Patterson GH, Jaiswal JK, Colberg-Poley AM. 2017. Superresolution imaging identifies that conventional trafficking pathways are not essential for endoplasmic reticulum to outer mitochondrial membrane protein Transport. Sci Rep. 7 (1):16.
Kwon D, Park E, Sesaki H, Kang SJ. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission. 2017. Biochem Biophys Res Commun. 493(1):737-743
Yamada T, Adachi Y, Fukaya M, Iijima M, Sesaki H. 2016. Dynamin-Related Protein 1 Deficiency Leads to Receptor-Interacting Protein Kinase 3-Mediated Necroptotic Neurodegeneration. 2016. Am J Pathol. Nov;186(11):2798-2802.
Manczak M, Kandimalla R, Fry D, Sesaki H, Reddy PH. 2016. Protective Effects of Reduced Dynamin-related Protein 1 Against Amyloid Beta-induced Mitochondrial Dysfunction and Synaptic Damage in Alzheimer's Disease. Hum Mol Genet. 25(23):5148-5166.
Kandimalla R, Manczak M, Fry D, Suneetha Y, Sesaki H, Reddy PH. 2016. Reduced Dynamin-related Protein 1 Protects Against Phosphorylated Tau-induced Mitochondrial Dysfunction and Synaptic Damage in Alzheimer's Disease. Hum Mol Genet. 25(22):4881-4897.
Kojima R, Kajiura S, Sesaki H, Endo T, Tamura Y. 2016. Identification of multi-copy suppressors for ER-mitochondria tethering proteins in Saccharomyces cerevisiae. FEBS Lett. 2016; Epub ahead of print.
Adachi Y, Itoh K, Yamada T, Cerveny KL, Suzuki TL, Macdonald P, Frohman MA, Ramachandran R, Iijima M, Sesaki H. Coincident phosphatidic acid interaction restrains Drp1 in mitochondrial division. Mol Cell. 2016;63:1034-43.
Xiong ZM, Choi J, Wang K, Zhang H, Tariq Z, Wu D, Ko E, LaDana, C, Sesaki H, Cao K. Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria. Aging Cell. 2016;15:279-290
Zhang L, Trushin S, Christensen TA, Bachmeier BV, Gateno B, Schroeder A, Yao J, Itoh K, Sesaki H, Poon WW, Gylys KH, Patterson ER, Parisi JE, Diaz Brinton R, Salisbury JL, Trushina E. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. Sci Rep. 2016;6:18725
Senoo H, Cai H, Wang Y, Sesaki H, Iijima M. The novel racE binding protein GflB sharpens ras activity at the leading edge of migrating cells. Mol Biol Cell. 2016;27(10):1596-605.
Roy M, Itoh K, Iijima M, Sesaki H. Parkin suppresses Drp1-independent mitochondrial division. Biochem Biophys Res Commun. 2016;475(3):283-8.
Khacho M, Clark A, Svoboda DS, Azzi J, MacLaurin JG, Meghaizel C, Sesaki H, Lagace DC, Germain M, Harper M-E, Park DS, Slack RS. 2016. Mitochondrial dynamics impact stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell. 19(2):232-47.
Buck MD, O'Sullivan D, Klein Geltink RI, Curtis JD, Chang CH, Sanin DE, Qiu J, Kretz O, Braas D, van der Windt GJ, Chen Q, Huang SC, O'Neill CM, Edelson BT, Pearce EJ, Sesaki H, Huber TB, Rambold AS, Pearce EL. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell. 2016;Epub ahead of print
Klionsky DJ et al. (~ 2000 authors). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12:1-222
Yamada T, Adachi Y, Iijima M, Sesaki H. Making a division apparatus on mitochondria. Trends Biochem Sci. 2016;41:209-210
Senoo H, Sesaki H, Iijima M. A GPCR handles bacterial sensing in chemotaxis and phagocytosis. Dev Cell. 2016;36:354-356.
Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K, Berg-Alonso L, Kageyama Y, Serre V, Moore D, Verschueren A, Rouzier A, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklingerm V. Reply: High prevalence of CHCHD10 mutations in patients with frontotemporal dementia from China. Brain. 2016;Epub ahead of print
Genin EC, Plutino M, Bannwarth S, Villa E, Cisneros-Barroso E, Roy M, Ortega-Vila B, Fragaki K, Lespinasse F, Pinero-Martos E, Augé G, Moore D, Burté F, Lacas-Gervais S, Kageyama Y, Itoh K, Yu-Wai-Man P, Sesaki H, Ricci JE, Vives-Bauza C, Paquis-Flucklinger V. CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis. EMBO Mol Med. 2015;8:58-72
Roy, M., Reddy, P.H., Iijima, M., and Sesaki, H. (2015). Mitochondrial division and fusion in metabolism. Curr. Opin. Cell Biol. 33:111-118
Serasinghe, M.N., Weider, S.Y., Renault, T.T., Elkholi, R., Asciolla, J.J., Yao, J.L., Jabado, O., Hoehn, K., Kageyama, Y., Sesaki, H., and Chipuk, J.E. (2015). Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol. Cell. 57: 521-536.
Li, S., Xu, S., Roelofs, B.A., Boyman, L., Lederer, J.W., Sesaki, H., and Karbowski, M. (2015). Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission. J. Cell Biol. 208: 109-123.
Kageyama, Y., Hoshijima, M., Seo, K., Bedja, D., Sysa-Shah, P., Andrabi, S., Chen, W., Höke, A., Dawson, V.L., Dawson, T.M., Gabrielson, K., Kass, D.A., Iijima, M., and Sesaki, H. (2014). Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain. EMBO J. 33: 2798-2813.
Berthet, A., Margolis, E.B., Zhang, J., Hsieh, I., Zhang, J., Hnasko, T.S., Ahmad, J., Edwards, R.H., Sesaki, H., Huang, E.J., and Nakamura K. (2014). Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons. J. Neurosci. 34: 14304-14317.
Zhang, Q., Tamura, Y., Roy, M., Adachi, Y., and Iijima, M., and Sesaki, H. (2014). Biogenesis and roles of phospholipids in mitochondrial fusion, division and mitophagy. Cell Mol. Life Sci. 71: 3767-3778.
Sesaki, H., Adachi, Y., Kageyama, Y., Itoh, K., and Iijima, M. (2014). In vivo functions of Drp1: Lessons learned from yeast genetics and mouse knockouts. Biochim Biophys Acta. 1842: 1179-1185.
Adachi, Y. and Sesaki, H. (2014). Cyclin C: An inducer of mitochondrial division hidden in the nucleus. Developmental Cell. 28: 112-114
Adachi, Y. and Sesaki, H., (2014). Cyclin C: Mitochondrial division inducer hidden in the nucleus. Developmental Cell. 28: 112-114
Itoh, K., Tamura, Y., Iijima, M., and Sesaki H. (2013). Effects of Fcj1-Mos1 and mitochondrial division on aggregation of mitochondrial DNA nucleoids and organelle morphology. Mol. Biol. Cell. 24: 1842-1851
Sesaki, H., Adachi, Y., Kageyama, Y., Itoh, K., and Iijima, M. (2013). In vivo functions of Drp1: Lessons learned from yeast genetics and mouse knockouts. Biochim Biophys Acta. Epub ahead of print.
Tamura, Y., Harada, Y., Nishikawa, S., Yamano, K., Megumi, K., Shiota, T., Kuroda, T., Kuge, O., Sesaki, H., Imai, K., Tomii, K., and Endo, T. (2013). Tam41 is a novel CDP-diacylglycerol synthase for cardiolipin biosynthesis in mitochondria. Cell Metabolism. 17: 709-18.
Kageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T.W., Reddy, P.H., Iijima, M. and Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J. Cell Biol. 197(4):535-51.
Tamura, Y., Onguka, O., Itoh, K., Endo, T., Iijima, M., Claypool, S.M., and Sesaki, H. (2012). Phosphatidylethanolamine biosynthesis in mitochondria: phosphatidylserine (PS) trafficking is independent of a PS decarboxylase and intermembrane space proteins, Ups1p and Ups2p. J. Biol. Chem. 287:43961-43971
Tamura, Y., Onguka, O., Aiken Hobbs, A.E., Jensen, R.E., Iijima, M., Claypool, S.M., and Sesaki, H. (2012). Role for two conserved intermembrane space proteins, Ups1p and Up2p, in intra-mitochondrial phospholipid trafficking. J. Biol. Chem. 287(19):15205-15218.
Tamura, Y., Itoh, K. and Sesaki, H. (2011). SnapShot: Mitochondrial dynamics. Cell. 145:1158-11581e
Zhang, Z., Wakabayashi, N., Wakabayashi, J., Tamura, Y., Song, W.-J., Sereda, S., Clerc, P., Polster, B.M., Aja, S.M., Pletnikov, M.V., Kensler, T.W., Shirihai, O.S.,., Iijima, M., Hussain, M., and Sesaki, H. (2011). The Dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells. Mol. Biol. Cell. 22: 2235-2245.
Tamura, Y., Iijima, M., and Sesaki, H. Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation. EMBO J. (2010). 29: 2875-2887.
Wakabayashi, J., Zhang, Z., Wakabayashi, N., Tamura, Y., Fukaya, M., Kensler, T.W., Iijima, M., and Sesaki, H. (2009). The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186: 805-816
Tamura, Y., Endo, T., , Iijima, M. and Sesaki, H. (2009). Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. J. Cell Biol. 185: 1029-1045
Cerveny, K.L., Studer, S.L., Jensen, R.E., and Sesaki, H. (2007). Yeast mitochondrial division and distribution requires the cortical Num1 protein. Developmental Cell. 12: 363-375.
Sesaki, H. Dunn, C.D., Iijima, M., Shepard, K.A., Yaffe, M.P., Machamer, C.E., and Jensen, R.E. (2006). Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of Mgm1p. J. Cell Biol. 173: 651-658.
Sesaki, H. and Jensen, R.E. (2001). UGO1 encodes an outer membrane protein required for mitochondrial fusion. J Cell Biol. 152:1123-34.
Sesaki, H. and Jensen, R.E. (1999). Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 147: 699-706.
To connect basic discovery with human health, we translate these findings into mammalian systems using genetically engineered mouse models and precise genome editing approaches. Our research integrates biochemical reconstitution, state-of-the-art imaging, and multi-omics analyses to understand how mitochondrial structure influences energy metabolism, mitophagy, and innate immune responses. By studying these processes in models of neurodegeneration, metabolic disease, heart failure, and cancer, our work aims to uncover fundamental mechanisms of mitochondrial regulation and identify new strategies for therapeutic intervention.