Beyond mitophagy: cytosolic PINK1 as a messenger of mitochondrial health.

Significance: Disruptions in mitochondrial homeostasis are implicated in human diseases across the lifespan. Recessive mutations in PINK1, which encodes the mitochondrially targeted PTEN-induced putative kinase 1 (PINK1), cause an autosomal recessive form of Parkinson's disease. As with all kinases, PINK1 participates in multiple functional pathways, and its dysregulation has been implicated in a growing number of diseases.

ERKed by LRRK2: a cell biological perspective on hereditary and sporadic Parkinson's disease.

The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD); mutations in LRRK2 account for up to 40% of PD cases in some populations. LRRK2 is a large protein with a kinase domain, a GTPase domain, and multiple potential protein interaction domains. As such, delineating the functional pathways for LRRK2 and mechanisms by which PD-linked variants contribute to age-related neurodegeneration could result in pharmaceutically tractable therapies.

Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells.

Recognition of injured mitochondria for degradation by macroautophagy is essential for cellular health, but the mechanisms remain poorly understood. Cardiolipin is an inner mitochondrial membrane phospholipid. We found that rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused externalization of cardiolipin to the mitochondrial surface in primary cortical neurons and SH-SY5Y cells.