title: Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins.
abstract: Mitochondria in mammals are organized into tubular networks that undergo frequent shape change. Mitochondrial fission and fusion are the main components mediating the mitochondrial shape change. Perturbation of the fission/fusion balance is associated with many disease conditions. However, underlying mechanisms of the fission/fusion balance are not well understood. Mitochondrial fission in mammals requires the dynamin-like protein DLP1/Drp1 that is recruited to the mitochondrial surface, possibly through the membrane-anchored protein Fis1 or Mff. Additional dynamin-related GTPases, mitofusin (Mfn) and OPA1, are associated with the outer and inner mitochondrial membranes, respectively, and mediate fusion of the respective membranes. In this study, we found that two heptad-repeat regions (HR1 and HR2) of Mfn2 interact with each other, and that Mfn2 also interacts with the fission protein DLP1. The association of the two heptad-repeats of Mfn2 is fusion inhibitory whereas a positive role of the Mfn2/DLP1 interaction in mitochondrial fusion is suggested. Our results imply that the differential binding of Mfn2-HR1 to HR2 and DLP1 regulates mitochondrial fusion and that DLP1 may act as a regulatory factor for efficient execution of both fusion and fission of mitochondria.
authors.affiliation: Mitochondrial Research and Innovation Group, Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Pinwei
authors.initials: P
authors.lastname: Huang
authors.forename: Chad A
authors.initials: CA
authors.lastname: Galloway
authors.forename: Yisang
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D053140:Organelle Shape; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000603499:mitochondrial fission factor, mouse; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse