Topology-dependent, bifurcated mitochondrial quality control under starvation

Area of Science:

• Cell Biology
• Autophagy Research
• Mitochondrial Dynamics

Background:

• Selective mitochondrial elimination via autophagy is vital for cellular processes.
• Existing pathways like PINK1-PRKN/PARKIN and receptor-dependent mechanisms are known.
• The principles guiding mitochondrial selection for autophagy remain unclear.

Purpose of the Study:

• To investigate a novel mechanism of selective mitochondrial elimination based on organellar topology.
• To understand how mitochondrial shape influences its fate under serum starvation.
• To elucidate the molecular basis for topology-dependent mitochondrial recycling.

Main Methods:

• Observation of mitochondrial topological transformations under serum starvation.
• Assessment of mitochondrial membrane potential and PRKN recruitment.
• Analysis of autophagosome receptor recruitment (CALCOCO2/NDP52, OPTN) in different mitochondrial populations.

Main Results:

• Mitochondria adopt distinct topologies: swollen or donut shapes, under serum starvation.
• Swollen mitochondria exhibit membrane potential dissipation and PRKN recruitment, leading to autophagy.
• Donut-shaped mitochondria maintain membrane potential and resist autophagy, even after depolarization, by preventing receptor recruitment.

Conclusions:

• Mitochondrial topology dictates its fate, with swollen forms being eliminated and donut forms being recycled.
• This topology-dependent mechanism represents a novel form of mitochondrial quality and quantity control under starvation.
• Donut mitochondria resist autophagy through mechanisms that prevent autophagosome receptor engagement, even when depolarized.