Background

Our cells depend on tiny energy factories called mitochondria to stay healthy. When mitochondria become damaged, cells remove them through a process called mitophagy. This system is especially important in neurons, where problems with mitochondrial quality control are linked to diseases such as Parkinson’s, Alzheimer’s, ALS, and frontotemporal dementia.

A protein called p62 can gather into droplet‑like structures inside cells through a process known as phase separation. These p62 droplets help maintain protein quality by managing misfolded or aggregated proteins. However, it has been unclear whether p62 droplets also play a role in maintaining the quality of mitochondria.

Research

In this study, we used a light‑controlled “OptoDroplet” system to investigate how p62 droplets form inside cells. Surprisingly, we found that when p62 undergoes phase separation, it clusters damaged mitochondria together. This clustering appears to regulate how quickly mitochondria are targeted for removal during PINK1/Parkin‑mediated mitophagy. We also discovered that ALS‑associated mutations in p62 disrupt this clustering process.

Impact

Our findings reveal a new role for p62 droplets: they help control mitochondrial quality by influencing how damaged mitochondria are organised and processed. Understanding this could give new insights into how cells manage energy and why mitochondria-related problems happen in neurodegenerative diseases.