MIRO‐1 interacts with VDAC‐1 to regulate mitochondrial membrane potential in Caenorhabditis elegans

Precise regulation of mitochondrial fusion and fission is essential for cellular activity and animal development. Imbalances between these processes can lead to fragmentation and loss of normal membrane potential in individual mitochondria. In this study, we show that MIRO‐1 is stochastically elevated in individual fragmented mitochondria and is required for maintaining mitochondrial membrane potential. We further observe a higher level of membrane potential in fragmented mitochondria in fzo ‐ 1 mutants and wounded animals. Moreover, MIRO‐1 interacts with VDAC‐1, a crucial mitochondrial ion channel located in the outer mitochondrial membrane, and this interaction depends on the residues E473 of MIRO‐1 and K163 of VDAC‐1. The E473G point mutation disrupts their interaction, resulting in a reduction of the mitochondrial membrane potential. Our findings suggest that MIRO‐1 regulates membrane potential and maintains mitochondrial activity and animal health by interacting with VDAC‐1. This study provides insight into the mechanisms underlying the stochastic maintenance of membrane potential in fragmented mitochondria. Synopsis MIRO‐1 interacts with VDAC‐1 to modulate its activity and regulate mitochondrial membrane potential in C. elegans , which provides mechanistic insight into the stochastic maintenance of activity in fragmented mitochondria. MIRO‐1 levels are elevated in individual fragmented mitochondria. MIRO‐1 is required for the maintenance of mitochondrial membrane potential. MIRO‐1 interacts with VDAC‐1 to regulate mitochondrial membrane potential. MIRO‐1 regulates VDAC‐1 activity via their direct interaction. Graphical Abstract MIRO‐1 interacts with VDAC‐1 to modulate its activity and regulate mitochondrial membrane potential in C. elegans , which provides mechanistic insight into the stochastic maintenance of activity in fragmented mitochondria.