IRGM promotes the PINK1-mediated mitophagy through the degradation of Mitofilin in SH-SY5Y cells.

Mitochondria is a double membrane-bound cellular organelle that generates energy to maintain the homeostasis of cells. Immunity-related GTPase M (IRGM) in human locates at the inner membrane of mitochondria and is best known for its role in regulating autophagy against intracellular pathogens. Previous studies have shown that IRGM is crucial for the normal function of mitochondria, yet, the molecular mechanisms underlying IRGM-mediated quality control of mitochondria are still not fully understood. In this study, we showed that knocking-down IRGM inhibits CCCP induced mitophagy in SH-SY5Y cells. Furthermore, we reported that IRGM decreases the stability of Mitofilin (IMMT, MIC60) in the damaged mitochondria. Knocking down Mitofilin rescues the loss of mitophagy that is observed in the IRGM KD cells, suggesting that IRGM regulates mitophagy through the inhibition of Mitofilin. These data together provide molecular insight regarding how IRGM regulates mitophagy to control the quality of mitochondria.