FIGURE 1.

A summary of altered mitochondrial mechanisms in multiple neurodegenerative diseases. (A) Normally, peptides targeted for the mitochondrial matrix move through the TOM complex on the outer mitochondrial membrane, then through the TIM23 complex, where mitochondrial chaperones assist in proper folding and processing enzymes cleave peptides, allowing them to mature. Various proteinopathies alter efficiency of mitochondrial protein import at either the outer or inner membrane, while others are characterized by reduced protease activity. Impaired import results in protein aggregation within mitochondria or the surrounding cytosol, chronically activating mitochondrial quality control mechanisms. (B) Mitochondrial fission is mediated by oligomers of Drp1 that constrict the organelle; fusion of the outer mitochondrial membranes is mediated primarily by Mfn1 and Mfn2, while fusion of the inner mitochondrial membrane is mediated by OPA1. A common characteristic of these neurodegenerative diseases is an increase in fission and a decrease in fusion. This leads to fragmentation of mitochondria, reducing their efficiency. (C) Mitophagy is commonly inhibited in proteinopathies; this leads to accumulation of damaged mitochondria.