Significance of Mitochondrial Protein Post-translational Modifications in Pathophysiology of Brain Injury

Mitochondria are complex organelles that undergo constant fusion and fission in order to adapt to the ever-changing cellular environment. The fusion/fission proteins, localized in the inner and outer mitochondrial membrane, play critical roles under pathological conditions such as acute brain injury and neurodegenerative diseases. Post-translational modifications of these proteins tightly regulate their function and activity, ultimately impacting mitochondrial dynamics and their efficiency to generate ATP. The individual post-translational modifications that are known to affect mitochondrial dynamics include SUMOylation, ubiquitination, phosphorylation, S-nitrosylation, acetylation, O-linked N-acetyl-glucosamine glycosylation, ADP-ribosylation, and proteolytic cleavage. Under stress or pathologic conditions, several of these modifications are activated leading to a complex regulatory mechanism that shifts the state of the mitochondrial network. The main goal is to accommodate and adapt the cellular bioenergetics metabolism to the energetic demand of the new extra- and/or intracellular environment. Understanding the complex relationship between these modifications on fusion and fission proteins in particular pathologic stress or diseases can provide new promising therapeutic targets and treatment approaches. Here, we discuss the specific post-translational modifications of mitochondrial fusion/fission proteins under pathologic conditions and their impact on mitochondrial dynamics.