Because mitochondria are so important for survival, cells have developed a specialized information pipeline, called mitochondrial retrograde signaling pathways, to get periodic updates on their mitochondria’s health. One of these pathways evaluates mitochondrial fitness by sensing how much mitochondrial DNA (mtDNA) is present in the cell—low levels of mtDNA can signal mitochondrial stress and encourage inflammation. Until now, the pathway controlling mtDNA sensing in mammalian cells was poorly understood.
Research from Professor Gerald Shadel, postdoctoral researcher Alva Sainz, and colleagues identified the protein FAM43A as an early responder to mtDNA depletion in mammalian cells. When FAM43A levels are suddenly reduced, a mitochondrial rescue mission ensues, increasing mitochondrial mass and rescuing mtDNA levels. Their findings enrich scientific understanding of mitochondrial stress, which could inform future treatments for many neurological, metabolic, and aging-related disorders.
