The Decline of Mitophagy in Age-Related Neurodegenerative Conditions
Mitochondria are the power plants of the cell. A herd of these bacteria-like organelles in every cell manufacture the chemical energy store molecules that are used to power cellular processes. Mitochondrial function declines with age throughout the body. Evidence suggests that this is due to changes in mitochondrial dynamics that inhibit the quality control mechanisms of mitophagy that are responsible for recycling worn and damaged mitochondria. This loss of miochondrial function is well known to contribute to the progression of neurodegenerative conditions, as the brain is an energy-hungry organ, making this an important aspect of aging to target for reversal.
Mitochondrial health is vital for cellular and organismal homeostasis, and mitochondrial defects have long been linked to the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, ALS, Huntington's, and others. However, it is still unclear whether cellular mechanisms required for the maintenance of mitochondrial integrity and function are deficient in these diseases, thus exacerbating mitochondrial pathology. The quality control of mitochondria involves multiple levels of strategies to protect against mitochondrial damage and maintain a healthy mitochondrial population within cells. In neurons, mitophagy serves as a major pathway of the quality control mechanisms for the removal of aged and defective mitochondria through lysosomal proteolysis. The molecular and cellular mechanisms that govern mitophagy have been extensively studied in the past decade. However, mitophagy deficit has only been recognized recently as a key player involved in aging and neurodegeneration.
Given the fact that mitochondrial deficit is clearly linked to neuronal dysfunction and the exacerbation of disease defects, protection of mitochondrial function could be a practical strategy to promote neuroprotection and modify disease pathology. Mitochondrially targeted antioxidants have been proposed. In particular, the antioxidant MitoQ, a redox active ubiquinone targeted to mitochondria, has been examined and demonstrated to have positive effects in multiple models of aging and neurodegenerative disorders. Importantly, mitophagy could be another promising target for drug discovery strategy. Therefore, further detailed studies to elucidate mitophagy mechanisms not only advance our understanding of the mitochondrial phenotypes and disease pathogenesis, but also suggest potential therapeutic strategies to combat neurodegenerative diseases.
I would say that decline in mitophagy does not only reduce the mitochondrial function. It also leads to an increased reactive oxygen species load and by extension to inflammation