Mitochondria are important in aging; some forms of damage to these organelles can produce sweeping detrimental effects when they evade quality control mechanisms. There are hundreds of mitochondria inside any given cell, and the related quality control mechanisms are thought to usually involve the destruction of an entire mitochondrion. Here researchers detail a less drastic mechanism that may act to clear damaged proteins from mitochondrial structures:
Mitochondria provide cells with energy and metabolite molecules that are essential for cell growth, and faulty mitochondria cause a number of severe genetic and age-related diseases. To maintain mitochondria in a fully working state, cells have evolved a range of quality control systems for them. For example, faulty mitochondria can be removed through a process called mitophagy. In this process, which is similar to autophagy (the process used by cells to degrade unwanted proteins and organelles), the entire mitochondrion is enclosed by a double membrane. In yeast cells this structure fuses with a compartment called the vacuole, where various enzymes degrade and destroy the mitochondrion. In animal cells an organelle called the lysosome takes the place of the vacuole. Now researchers report evidence for a new quality control mechanism that helps to protect mitochondria from age- and stress-related damage in yeast. In this mechanism, a mitochondrion can selectively remove part of its membrane to send the proteins embedded in this region to the lysosome/vacuole to be destroyed, while leaving the remainder of the mitochondrion intact.
Researchers tracked the fate of Tom70, a protein that is found in the outer membrane of mitochondria, and discovered that it accumulated in the vacuole as the yeast aged. This accumulation was not the result of mitophagy, as Tom70 was directed to the vacuole even when a gene required for mitophagy was absent. Previous reports have linked cellular aging to a decline in mitochondrial activity, which is caused by an earlier loss of pH control in the vacuole. For this reason, researchers tested whether a drug that disrupts the pH of the vacuole triggers the degradation of Tom70. This appears to be the case - the drug caused Tom70 to move from the mitochondria to the vacuole for degradation.
Before Tom70 ended up in the vacuole it accumulated in a mitochondrial-derived compartment (MDC) at the surface of the mitochondria, close to the membrane of the vacuole. The formation of this compartment depended on the machinery that drives the process by which mitochondria divide. However, the subsequent delivery of the contents of the MDC to the vacuole used factors that are required for the late stages of autophagy. The researchers found that the MDC contained Tom70 and 25 other proteins, all of which are mitochondrial membrane proteins that rely on Tom70 to import them into the mitochondrial membrane. This suggests that the MDC degradation pathway selectively removes a specific group of mitochondrial proteins. The researchers hypothesize that MDC formation is linked to metabolite imbalance, as the loss of acidity inside the vacuole prevents amino acids from being stored there. This in turn leads to a build up of amino acids in the cytoplasm that can overburden the transport proteins that import them into the mitochondria. In this scenario, the selective degradation of mitochondrial transport proteins by the MDC pathway can be seen as a response that protects the organelle against an unregulated, and potentially harmful, influx of amino acids.