Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction

摘要: Mitochondria undergo continual cycles of fusion and fission, the balance these opposing processes regulates mitochondrial morphology. Paradoxically, cells invest many resources to maintain tubular morphology, when reducing both fission simultaneously achieves same end. This observation suggests a requirement for fusion, beyond maintenance organelle Here, we show that with targeted null mutations in Mfn1 or Mfn2 retained low levels escaped major cellular dysfunction. Analysis mutant showed homotypic heterotypic interactions Mfns are capable fusion. In contrast, lacking completely lacked severe defects, including poor cell growth, widespread heterogeneity membrane potential, decreased respiration. Disruption OPA1 by RNAi also blocked all resulted similar defects. These defects Mfn-null OPA1-RNAi mammalian were corrected upon restoration unlike irreversible found fzo yeast. fragmentation mitochondria, without loss did not result such Our results key functions decline as is progressively abrogated.