Our Science: PINK1
Mitochondria: A common thread in neurodegeneration
Mitochondria are well known for their role in generating the ATP our cells need to survive. What’s less appreciated, but critical to their role in neurodegenerative disease, is the role of mitochondria in inflammation, proteostasis, and cell death.
PINK1: A master regulator of mitochondrial quality control
PINK1 is the cell’s surveillance system for damaged mitochondria. An unusual kinase, it only stabilizes in the presence of a depolarized mitochondrion; once stabilized, it activates a mitophagy pathway that leads to clearance of the damaged organelle. PINK1 activation has been shown to oppose the inflammation, mtDNA mutations, and metabolic/proteostatic failures that can lead to cell death in disease.
Mitophagy: A protective mechanism for cellular homeostasis
Multiple recent studies have shown that pathogenic protein species implicated in neurodegenerative diseases (eg, alpha synuclein, beta amyloid, tau, and TDP43) can associate with mitochondria and drive mitochondrial dysfunction. Mitophagy, the process by which cells clear their damaged mitochondria, plays an important protective role in these circumstances: not only is the normal, healthy mitochondrial pool restored, but the proteotoxic species are cleared along with the bad mitochondria. Mitokinin’s scientists have shown that by potentiating the PINK1 pathway in times of proteotoxic stress, neuron health can be restored and disease-driving pathologies reduced or eliminated.
A therapeutic approach for multiple diseases
