Magmas functions as a ROS regulator and provides cytoprotection against oxidative stress-mediated damages

Cell Death Dis. 2014 Aug 28;5(8):e1394. doi: 10.1038/cddis.2014.355.

Abstract

Redox imbalance generates multiple cellular damages leading to oxidative stress-mediated pathological conditions such as neurodegenerative diseases and cancer progression. Therefore, maintenance of reactive oxygen species (ROS) homeostasis is most important that involves well-defined antioxidant machinery. In the present study, we have identified for the first time a component of mammalian protein translocation machinery Magmas to perform a critical ROS regulatory function. Magmas overexpression has been reported in highly metabolically active tissues and cancer cells that are prone to oxidative damage. We found that Magmas regulates cellular ROS levels by controlling its production as well as scavenging. Magmas promotes cellular tolerance toward oxidative stress by enhancing antioxidant enzyme activity, thus preventing induction of apoptosis and damage to cellular components. Magmas enhances the activity of electron transport chain (ETC) complexes, causing reduced ROS production. Our results suggest that J-like domain of Magmas is essential for maintenance of redox balance. The function of Magmas as a ROS sensor was found to be independent of its role in protein import. The unique ROS modulatory role of Magmas is highlighted by its ability to increase cell tolerance to oxidative stress even in yeast model organism. The cytoprotective capability of Magmas against oxidative damage makes it an important candidate for future investigation in therapeutics of oxidative stress-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / toxicity
  • Arsenites / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • DNA, Mitochondrial / analysis
  • Electron Transport Chain Complex Proteins / metabolism
  • HEK293 Cells
  • HSP70 Heat-Shock Proteins / metabolism
  • HeLa Cells
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Oxidative Stress / drug effects
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism*
  • Sodium Compounds / toxicity

Substances

  • Arsenites
  • DNA, Mitochondrial
  • Electron Transport Chain Complex Proteins
  • HSP70 Heat-Shock Proteins
  • Mitochondrial Proteins
  • PAM16 protein, human
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Sodium Compounds
  • sodium arsenite
  • Acetylcysteine