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Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis.

Authors
Lee, YJ; Jeong, SY; Karbowski, M; Smith, CL; Youle, RJ
Citation
Molecular biology of the cell, 15(11):5001-5011, 2004
Journal Title
Molecular biology of the cell
ISSN
1059-15241939-4586
Abstract
During apoptosis, the mitochondrial network fragments. Using short hairpin RNAs for RNA interference, we manipulated the expression levels of the proteins hFis1, Drp1, and Opa1 that are involved in mitochondrial fission and fusion in mammalian cells, and we characterized their functions in mitochondrial morphology and apoptosis. Down-regulation of hFis1 powerfully inhibits cell death to an extent significantly greater than down-regulation of Drp1 and at a stage of apoptosis distinct from that induced by Drp1 inhibition. Cells depleted of Opa1 are extremely sensitive to exogenous apoptosis induction, and some die spontaneously by a process that requires hFis1 expression. Wild-type Opa1 may function normally as an antiapoptotic protein, keeping spontaneous apoptosis in check. However, if hFis1 is down-regulated, cells do not require Opa1 to prevent apoptosis, suggesting that Opa1 may be normally counteracting the proapoptotic action of hFis1. We also demonstrate in this study that mitochondrial fragmentation per se does not result in apoptosis. However, we provide further evidence that multiple components of the mitochondrial morphogenesis machinery can positively and negatively regulate apoptosis.
MeSH terms
*ApoptosisDown-RegulationGTP Phosphohydrolases/*physiologyHela CellsHumansImmunoblottingImmunohistochemistryMembrane ProteinsMicroscopy, ConfocalMicrotubule-Associated Proteins/*physiologyMitochondria/*metabolismMitochondrial Proteins/*physiologyPoly(ADP-ribose) Polymerases/metabolismRNA/metabolismRNA InterferenceSubcellular FractionsTime Factors
DOI
10.1091/mbc.E04-04-0294
PMID
15356267
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
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