Mechanisms For Clearing Damaged Mitochondria

Damaged mitochondria accumulate in your cells with advancing age, and their malfunctions cause all sorts of further harm to your biochemistry. All in all they are a bad thing, and a strong candidate for the most important cause of degenerative aging. So it is with interest I notice that researchers working on Parkinson's disease are uncovering more of the cellular mechanisms that - when working properly - cull damaged mitochondria so that they can be replaced:

Parkin, the product of the Parkinson's disease-related gene Park2, prompts neuronal survival by clearing the cell of its damaged mitochondria.


Several lines of evidence suggest that Parkin loss is associated with mitochondrial dysfunction, but exactly how was unknown. To learn more about Parkin's role in cells, Narendra et al. examined the protein's subcellular location. They found that Parkin was present in the cytoplasm of most cells, but translocated to mitochondria in cells that had undergone mitochondrial damage such as membrane depolarization.

Damaged mitochondria can trigger cell death pathways; indeed, dysregulation of mitochondrial health was already thought to be a possible cause of the neuronal cell death associated with Parkinson's disease. The relocation of Parkin to damaged mitochondria, the team showed, sends these defunct organelles to autophagosomes for degradation. Parkin may thus prevent the damaged mitochondria from triggering cell death. Because neurons are not readily replicable, disposing of damaged mitochondria may be especially important in the adult brain.

I'm not so interested in the association with Parkinson's, since the cell death mechanisms for the dopamine-producing neurons that die off in Parkinson's appear to be further downstream in the chain of cause and effect than accumulation of alpha-synuclin. I am, however, very interested any mechanism that shows potential for enhancement to clear out more damaged mitochondria.

If you look back at the details of how damaged mitochondria eventually replace undamaged mitochondria in a cell, however, it isn't clear whether Parkin is involved in such a mechanism. The crucial point is whether Parkin is only involved in responding to damage to mitochondrial membranes, as the type of internal mitochondrial damage that contributes to aging leaves the membranes intact. The devil, as always, is in the details - and biochemistry has no shortage of details.


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