FPU2025 - QUALITY CONTROL FOR LIFE: SELECTION OF HEALTHY MITOCHONDRIA IN GAMETOGENESIS

Mitochondria are essential for cellular energy and carry their own DNA, which is inherited maternally. Because each oocyte receives thousands of mitochondria—along with any mtDNA mutations—the germline must ensure the transmission of functional organelles. Yet the mechanisms guiding this selection remain poorly understood. Recent Drosophila studies show that the female germline preferentially retains mitochondria with higher energetic output, suggesting an early quality-control system. Fragmentation, depolarization, and mitophagy help eliminate defective organelles, but how these processes are coordinated is unclear. A promising clue is the association between mitochondria and the fusome, an ER-rich structure formed during early oogenesis. As ER-to-mitochondria calcium transfer enhances mitochondrial activity, the ER may actively assess mitochondrial fitness. This project proposes that the fusome acts as a regulatory hub where ER–mitochondria communication evaluates mitochondrial performance and influences inheritance. Using Drosophila genetics, we aim to: map ER–mitochondria contacts and dynamics; manipulate calcium flux to test its role in quality control; generate disease models with human mtDNA mutations; and identify genes driving mitochondrial selection. Understanding these processes could enable future strategies to reduce pathogenic mtDNA transmission.