The mitochondrial aspartate transporter Ucp4a regulates muscle aging and animal lifespan in Drosophila melanogaster

Mild distress of mitochondria extends animal lifespan, yet the underlying mechanisms are not completely understood. Here we screened mitochondrial proteins for effects on longevity and found that flies mutant in Uncoupling protein 4a (Ucp4a), which encodes a mitochondrial aspartate transporter, have extended lifespans. Tissue-specific experiments revealed knockdown of Ucp4a in muscles, but not neurons, fat, or intestine, to extend lifespan and also eliminate polyubiquitinated protein aggregates, which accumulate with aging and are associated with lifespan. These findings suggest a retrograde mitochondrial signaling process initiated by reduced cytosol aspartate level culminates in muscle protein aggregate removal and lifespan extension.