Mechanisms of Mitophagy Initiation: Formation and Function of Initiation Hubs

• Applicant: Professorin Dr. Claudine Kraft
• Subject Area: Biochemistry ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567190061

Autophagy is a fundamental cellular degradation process that targets protein complexes, aggregates, and organelles. While bulk autophagy non-specifically sequesters cytoplasmic material, selective autophagy employs specialized receptors for targeted degradation. A key form of selective autophagy, mitophagy, requires mitochondrial fission to separate parts of the mitochondrial network before degradation. However, the molecular mechanisms governing mitophagy initiation, and the connection between mitophagy and mitochondrial fission remain unclear. Our recent findings reveal that initiation hubs emerge as distinct foci on mitochondria containing the key autophagy player ULK1, which then recruit further essential components of the autophagy machinery. Mitochondrial recruitment of ULK1 is sufficient to trigger initiation hub formation and drive mitophagy. This project aims to characterize the composition and function of these initiation hubs, elucidate their role in linking mitophagy to mitochondrial fission, and unravel ULK1’s contribution to this process. Using fluorescence microscopy and biochemical assays, we will dissect the hierarchical assembly of initiation hubs and uncover novel regulatory mechanisms governing mitophagy initiation. These insights will advance our understanding of mitochondrial quality control and cellular homeostasis.

• DFG Programme: Research Grants