Mitochondria are the powerhouses of cells: They have a waste disposal mechanism to dispose of mutated mtDNA
Researchers have identified a molecular targeting that could lead to new therapeutic options for treating aging-related diseases such as Parkinson’s. Scientists from the University of Cologne discovered how cells can remove mutated mitochondrial (mtDNA). Mitochondria provide energy to our cells. They still contain genetic material in chromosomes-like structures, due to their evolution from bacteria. They transform the chemical energy from our food into biologically useful form. Researchers from the University of Cologne Physiology Centre, the Centre for Molecular Medicine Cologne and the CECAD Cluster of Excellence for Aging Research have now demonstrated that mutations of mtDNA result in a local rearrangement of protein within the mitochondrial membrane. The mutated mitochondrial DNA is then targeted, removed, and submitted to autophagy – the cellular \”waste disposal\”. The findings were published in Nature Communications with the title \”Mitochondrial Membrane Proteins and VPS35 orchestrate select removal of mtDNA\”.
As we age, mtDNA mutations accumulate in many tissues. Many diseases associated with aging are caused by these mutations. Every cell contains thousands of copies of mtDNA, and mitochondrial function can only be impaired when the number of mutant mtDNA molecules reaches a threshold. Mitophagy is triggered by mitochondrial damage including acute mtDNA injury. This has been known for a long time. This process involves selective degradation and recycling of dysfunctional mitochondrial components.
David Pla-Martin, lead author of this study, explained that the mechanism doesn’t affect the cells’ mitochondrial endowment, but instead only removes the damaged mtDNA. We showed, by labeling neighbouring proteins (so-called proximity labelling), that mtDNA damages lead to the recruitment endosomes close to nucleoids. This also prevents an immune response. Pla-Martin said that the protein VPS35 is the main component of retromer and mediates maturation of endosomes to late autophagy vasculae, where recycling and degradation ultimately occur.
Source:
Powerhouses of the Cells: Mitochondria have a Waste Disposal Mechanism to get rid of Mutated mtDNA
