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

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.

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38

“…Several enzymes SOD, GPx, and CAT are associated with the removal of these free radical species within cells. If these enzymes are damaged by several occurrences of oxidative stress, degenerative diseases can result31. Cytosolic superoxide (O 2 − ) is generated by the one-electron reduction of O 2 through the slippage of electrons from the electron carriers of the mitochondrial electron transport chain.…”

Functional Diversity of Human Mitochondrial J-proteins Is Independent of Their Association with the Inner Membrane Presequence Translocase

“…J and K, yeast cells were incubated untreated (J) or treated with 300 M cisplatin (K), and the growth of cells were monitored at 30°C. mas, thus suggesting a possible role of JC15⅐Magmas subcomplex in regulation of respiratory activity (22,34). Moreover, a specific loss of expression of JC15, especially in tissues of epithelial origin, results in development of chemoresistance against various chemotherapeutic drugs (30).…”

“…Homologs of Pam16 and Pam18-like proteins are found across all eukaryotic species. The ortholog of Pam16, identified in humans as Magmas, is essential for biogenesis of mitochondria and also plays an additional role in regulation of reactive oxygen species in humans (22). A recent observation showed Magmas to function as a ROS (reactive oxygen species) regulator where it maintains the cellular redox state under stress conditions by promoting efficient oxidative phosphorylation (OXPHOS) activity and enhanced reactive oxygen species scavenging (22).…”

Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability

“…Production of mitochondrial superoxide was further validated by fluorescence microscopy following previously published methods (24,26). Briefly, HeLa cells were treated with 1 M MitoSOX Red for 20 min and washed with 1ϫ PBS, followed by mounting in ProLong Gold Antifade reagent with DAPI (Invitrogen).…”