TOM20-driven E3 ligase recruitment regulates

Mitochondria, organelles essential for maintaining cellular energy balance and health, constantly change shape through fusion and fission—processes in which they join together and split apart, respectively. In a study published in Nature Chemical Biology, Dr. Itay Koren and his team discovered a new way cells regulate this dynamic. The researchers reveal a mechanism involving the E3 ligase complex CRL2-FEM1B, which is recruited to the outer mitochondrial membrane by TOM20. There, FEM1B targets the mitochondrial fusion factor PLD6 for ubiquitin-mediated degradation. Loss of FEM1B or disruption of its interaction with TOM20 impairs PLD6 turnover, leading to mitochondrial aggregation. Using structural and biochemical approaches, this work uncovers the basis of FEM1B-PLD6 recognition and establishes a TOM20-dependent mechanism for localizing E3 ligases to mitochondria. This insight into mitochondrial protein homeostasis may inform therapeutic strategies for diseases linked to dysfunctional mitochondrial dynamics.