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Review

Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters

1
Department of Mitochondrial Physiology, Institute of Physiology of the Czech Academy of Sciences, Vídeňská 1084, 14220 Prague, Czech Republic
2
Department of Pediatrics, Division of Neonatology, Columbia University William Black Building, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Nukhet Aykin-Burns
Antioxidants 2021, 10(5), 678; https://doi.org/10.3390/antiox10050678
Received: 26 February 2021 / Revised: 13 April 2021 / Accepted: 22 April 2021 / Published: 26 April 2021
(This article belongs to the Special Issue Mitochondrial Redox Regulations)
Patatin-like phospholipase domain-containing protein PNPLA8, also termed Ca2+-independent phospholipase A2γ (iPLA2γ), is addressed to the mitochondrial matrix (or peroxisomes), where it may manifest its unique activity to cleave phospholipid side-chains from both sn-1 and sn-2 positions, consequently releasing either saturated or unsaturated fatty acids (FAs), including oxidized FAs. Moreover, iPLA2γ is directly stimulated by H2O2 and, hence, is activated by redox signaling or oxidative stress. This redox activation permits the antioxidant synergy with mitochondrial uncoupling proteins (UCPs) or other SLC25 mitochondrial carrier family members by FA-mediated protonophoretic activity, termed mild uncoupling, that leads to diminishing of mitochondrial superoxide formation. This mechanism allows for the maintenance of the steady-state redox status of the cell. Besides the antioxidant role, we review the relations of iPLA2γ to lipid peroxidation since iPLA2γ is alternatively activated by cardiolipin hydroperoxides and hypothetically by structural alterations of lipid bilayer due to lipid peroxidation. Other iPLA2γ roles include the remodeling of mitochondrial (or peroxisomal) membranes and the generation of specific lipid second messengers. Thus, for example, during FA β-oxidation in pancreatic β-cells, H2O2-activated iPLA2γ supplies the GPR40 metabotropic FA receptor to amplify FA-stimulated insulin secretion. Cytoprotective roles of iPLA2γ in the heart and brain are also discussed. View Full-Text
Keywords: antioxidant synergy; mitochondrial phospholipase A2γ; mitochondrial uncoupling proteins; adenine nucleotide translocase; mitochondrial carriers; SLC25 gene family; lipid peroxidation; cytoprotection antioxidant synergy; mitochondrial phospholipase A2γ; mitochondrial uncoupling proteins; adenine nucleotide translocase; mitochondrial carriers; SLC25 gene family; lipid peroxidation; cytoprotection
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MDPI and ACS Style

Jabůrek, M.; Průchová, P.; Holendová, B.; Galkin, A.; Ježek, P. Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters. Antioxidants 2021, 10, 678. https://doi.org/10.3390/antiox10050678

AMA Style

Jabůrek M, Průchová P, Holendová B, Galkin A, Ježek P. Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters. Antioxidants. 2021; 10(5):678. https://doi.org/10.3390/antiox10050678

Chicago/Turabian Style

Jabůrek, Martin, Pavla Průchová, Blanka Holendová, Alexander Galkin, and Petr Ježek. 2021. "Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid–Conducting SLC25 Gene Family Transporters" Antioxidants 10, no. 5: 678. https://doi.org/10.3390/antiox10050678

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