Phase separation of C19orf12 regulates BNIP3 protein quality control and maintains neuronal mitophagy

Mutations in the C19orf12 gene are linked to mitochondrial membrane protein-associated neurodegeneration (MPAN).

• C19orf12 regulates the breakdown of the mitophagy receptor BNIP3 proteins via the lysosomal pathway.
• Disruption of this pathway leads to the buildup of oxidized BNIP3 proteins on mitochondria, hindering effective mitophagy.
• C19orf12 is involved in the formation of protein clusters that aid in the turnover of BNIP3 on the mitochondrial membrane.
• A rodent model of MPAN shows not only mitophagy deficiencies but also motor deficits and hallmark pathological features, including iron buildup and neuroinflammation.
• Impaired mitophagy is associated with the pathogenesis of MPAN, highlighting the importance of C19orf12 in mitochondrial quality control.

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