Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2 gamma with Fatty Acid-Conducting SLC25 Gene Family Transporters

0542843 - FGÚ 2022 RIV CH eng J - Článek v odborném periodiku
Jabůrek, Martin - Průchová, Pavla - Holendová, Blanka - Galkin, A. - Ježek, Petr
Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2 gamma with Fatty Acid-Conducting SLC25 Gene Family Transporters.
Antioxidants. Roč. 10, č. 5 (2021), č. článku 678. E-ISSN 2076-3921
Grant CEP: GA MŠMT(CZ) LTAUSA17174
Institucionální podpora: RVO:67985823
Klíčová slova: antioxidant synergy * mitochondrial phospholipase A2γ * mitochondrial uncoupling proteins * adenine nucleotide translocase * mitochondrial carriers * SLC25 gene family * lipid peroxidation * cytoprotection
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 7.675, rok: 2021
Způsob publikování: Open access
https://www.mdpi.com/2076-3921/10/5/678

Patatin-like phospholipase domain-containing protein PNPLA8, also termed Ca2+-independent phospholipase A2 gamma (iPLA2 gamma), 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, iPLA2 gamma 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 iPLA2 gamma to lipid peroxidation since iPLA2 gamma is alternatively activated by cardiolipin hydroperoxides and hypothetically by structural alterations of lipid bilayer due to lipid peroxidation. Other iPLA2 gamma roles include the remodeling of mitochondrial (or peroxisomal) membranes and the generation of specific lipid second messengers. Thus, for example, during FA beta-oxidation in pancreatic beta-cells, H2O2-activated iPLA2 gamma supplies the GPR40 metabotropic FA receptor to amplify FA-stimulated insulin secretion. Cytoprotective roles of iPLA2 gamma in the heart and brain are also discussed.
Trvalý link: http://hdl.handle.net/11104/0320184