Post-translational modification and mitochondrial function in Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease with currently no cure. Most PD cases are sporadic, and about 5–10% of PD cases present a monogenic inheritance pattern. Mutations in more than 20 genes are associated with genetic forms of PD. Mitochondrial dysfunction is considered a prominent player in PD pathogenesis. Post-translational modifications (PTMs) allow rapid switching of protein functions and therefore impact various cellular functions including those related to mitochondria. Among the PD-associated genes, Parkin, PINK1, and LRRK2 encode enzymes that directly involved in catalyzing PTM modifications of target proteins, while others like α-synuclein, FBXO7, HTRA2, VPS35, CHCHD2, and DJ-1, undergo substantial PTM modification, subsequently altering mitochondrial functions. Here, we summarize recent findings on major PTMs associated with PD-related proteins, as enzymes or substrates, that are shown to regulate important mitochondrial functions and discuss their involvement in PD pathogenesis. We will further highlight the significance of PTM-regulated mitochondrial functions in understanding PD etiology. Furthermore, we emphasize the potential for developing important biomarkers for PD through extensive research into PTMs.