Giant mitochondria do not fuse and exchange their contents with normal mitochondria.
Giant mitochondria accumulate within aged or diseased postmitotic cells as a consequence of insufficient autophagy, which is normally responsible for mitochondrial degradation. We report that giant mitochondria accumulating in cultured rat myoblasts due to inhibition of autophagy have low inner membrane potential and do not fuse with each other or with normal mitochondria. In addition to the low inner mitochondrial membrane potential in giant mitochondria, the quantity of the OPA1 mitochondrial fusion protein in these mitochondria was low, but the abundance of mitofusin-2 (Mfn2) remained unchanged. The combination of these factors may explain the lack of mitochondrial fusion in giant mitochondria and imply that the dysfunctional giant mitochondria cannot restore their function by fusing and exchanging their contents with fully functional mitochondria. These findings have important implications for understanding the mechanisms of accumulation of age-related mitochondrial damage in postmitotic cells.
Navratil
Marian
M
Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN, USA.
Terman
Alexei
A
Arriaga
Edgar A
EA
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology; D051381:Rats
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; C498811:Opa1 protein, rat