A Unified Mechanism For Mitochondrial Damage Sensing In Pink1-Parkin-Mediated Mitophagy

Researchers have discovered a common trigger for the cellular process that removes damaged mitochondria, finding that various types of mitochondrial damage all lead to a loss of mitochondrial membrane potential, which then activates the PINK1-Parkin pathway to initiate the removal process.

Our cells rely on tiny powerhouses called mitochondria to generate energy. When these mitochondria get damaged, they need to be removed to keep the cell healthy. This crucial clean-up process is called mitophagy, and it’s particularly important for preventing neurodegenerative diseases like Parkinson’s.

For a long time, scientists wondered if there was a single way cells recognized different kinds of mitochondrial damage to kickstart mitophagy. This new research reveals a unified mechanism: it turns out that many different forms of mitochondrial damage all lead to a collapse of the mitochondrial membrane potential (MMP). The MMP is essentially an electrical charge across the inner membrane of the mitochondria, vital for its normal function.

When the MMP is lost, a protein called PINK1, which is usually imported into healthy mitochondria and then broken down, gets stuck on the mitochondrial surface. This accumulation of PINK1 then acts as a signal to activate another protein called Parkin. Once activated, Parkin tags proteins on the outer surface of the damaged mitochondrion with small molecules called ubiquitin. These ubiquitin tags act like a “eat me” signal, marking the faulty mitochondrion for degradation and removal from the cell. This discovery provides a clearer understanding of how cells maintain mitochondrial health and could open new avenues for therapeutic interventions in diseases linked to mitochondrial dysfunction.

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Source: link to paper