Mitochondrial Protein PGAM5 Emerges as a New Regulator in Neurological Diseases.

Min-Zong Liang,Ting-Ling Ke,Linyi Chen

doi:10.3389/fnmol.2021.730604

Min-Zong Liang, Ting-Ling Ke + Show 1 more

Open Access

https://doi.org/10.3389/fnmol.2021.730604

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Abstract

As mitochondrial dysfunction has increasingly been implicated in neurological diseases, much of the investigation focuses on the response of the mitochondria. It appears that mitochondria can respond to external stimuli speedy fast, in seconds. Understanding how mitochondria sense the signal and communicate with cytosolic pathways are keys to understand mitochondrial regulation in diseases or in response to trauma. It was not until recently that a novel mitochondrial protein, phosphoglycerate mutase family member 5 (PGAM5) has emerged to be a new regulator of mitochondrial homeostasis. Although controversial results reveal beneficial as well as detrimental roles of PGAM5 in cancers, these findings also suggest PGAM5 may have diverse regulation on cellular physiology. Roles of PGAM5 in neuronal tissues remain to be uncovered. This review discusses current knowledge of PGAM5 in neurological diseases and provides future perspectives.

Highlights

Brain is an energy-expensive organ, consuming about 20 percent of our total energy (Rolfe and Brown, 1997)
phosphoglycerate mutase family member 5 (PGAM5) knockdown abolished the increase of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1-α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) induced by hemin (Hong and Lee, 2018). These results suggest that hemin enhances mitochondrial biogenesis via upregulating PGAM5
While regulation of PGAM5-nuclear respiratory factor 2 (NRF2) mediated mitochondrial biogenesis in neurological diseases had not been previously reported, a recent study revealed that interaction between PGAM5 and NRF2 resulted in blood–brain barrier disruption and neurological deficits in ischemic stroke (Gao et al, 2021)

Summary

Introduction

Brain is an energy-expensive organ, consuming about 20 percent of our total energy (Rolfe and Brown, 1997). Wang et al first demonstrated that PGAM5 regulated mitochondrial fission by dephosphorylating DRP1 in HeLa cells. PGAM5 dephosphorylated pDRP1(S637) and enhanced DRP1 activity whereas knockdown of PGAM5 prevented mitochondrial fission and necrosis in HeLa cells (Wang et al, 2012).

Results

Conclusion