PINK1/Parkin Mediated Mitophagy, Ca²⁺ Signalling, and ER–Mitochondria Contacts in Parkinson’s Disease

Abstract

Endoplasmic reticulum (ER)−mitochondria contact sites are critical structures for cellular function. They are implicated in a plethora of cellular processes, including Ca2+ signalling and mitophagy, the selective degradation of damaged mitochondria. Phosphatase and tensin homolog (PTEN)-induced kinase (PINK) and Parkin proteins, whose mutations are associated with familial forms of Parkinson’s disease, are two of the best characterized mitophagy players. They accumulate at ER−mitochondria contact sites and modulate organelles crosstalk. Alterations in ER−mitochondria tethering are a common hallmark of many neurodegenerative diseases including Parkinson’s disease. Here, we summarize the current knowledge on the involvement of PINK1 and Parkin at the ER−mitochondria contact sites and their role in the modulation of Ca2+ signalling and mitophagy.

Keywords

• pink1
• parkin
• mitophagy
• ca²⁺
• er–mitochondria tethering