Potential Role of Mic60/Mitofilin in Parkinson's Disease.

Victor S Van Laar,Teresa G Hastings,P Anthony Otero,Sarah B Berman

doi:10.3389/fnins.2018.00898

Abstract

There are currently no treatments that hinder or halt the inexorable progression of Parkinson’s disease (PD). While the etiology of PD remains elusive, evidence suggests that early dysfunction of mitochondrial respiration and homeostasis play a major role in PD pathogenesis. The mitochondrial structural protein Mic60, also known as mitofilin, is critical for maintaining mitochondrial architecture and function. Loss of Mic60 is associated with detrimental effects on mitochondrial homeostasis. Growing evidence now implicates Mic60 in the pathogenesis of PD. In this review, we discuss the data supporting a role of Mic60 and mitochondrial dysfunction in PD. We will also consider the potential of Mic60 as a therapeutic target for treating neurological disorders.

Highlights

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, was first described in 1817 by James Parkinson in “An Essay on the Shaking Palsy.” (Parkinson, 1817) In the 200 years that have passed since recognition of this neurological disorder, great strides have been made to characterize disease pathology, distinguish clinical symptoms, and develop a therapeutic treatment
Though the underlying mechanism of PD pathogenesis remains elusive, current ideology suggests that a combination of environmental exposure and genetic predisposition are responsible for most cases of PD (Horowitz and Greenamyre, 2010; Ritz et al, 2016)
Viability may be affected by the rearrangement of mitochondrial cristae, impaired mitochondrial respiration, impaired homeostasis, impaired fission and fusion, and disrupted protein import associated with Mic60 deficiency (John et al, 2005; Rabl et al, 2009; von der Malsburg et al, 2011; Bohnert et al, 2012; Zerbes et al, 2012a; Yang et al, 2015; Li et al, 2016; Van Laar et al, 2016)

Summary

Introduction

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, was first described in 1817 by James Parkinson in “An Essay on the Shaking Palsy.” (Parkinson, 1817) In the 200 years that have passed since recognition of this neurological disorder, great strides have been made to characterize disease pathology, distinguish clinical symptoms, and develop a therapeutic treatment. Independent studies from multiple labs have associated the inner mitochondrial membrane protein Mic60, known as mitofilin, with PD pathogenesis (Van Laar et al, 2008, 2009, 2016; Akabane et al, 2016; Tsai et al, 2018).

Results

Conclusion