Group VIA Phospholipase A2 Mitigates Palmitate-induced β-Cell Mitochondrial Injury and Apoptosis

Song, Houyan; Wohltmann, Mary; Tan, Mengxi; Ladenson, Jack H.; Turk, John

doi:10.1074/jbc.m114.561910

Cited by 31 publications

(25 citation statements)

References 111 publications

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“…If CL is not only translocated but also oxidized, it may trigger another program, which leads to apoptosis [26]. The mitochondrial phospholipase iPLA 2 β shows preference for oxidized CL molecules, which can protect cells against apoptotic death [73]. Monolyso-cardiolipin (MLCL), the product of this reaction can be re-acylated to CL by the enzyme ALCAT, which is located in the mitochondria-associated endoplasmic reticulum.…”

Section: Turnover Of CLmentioning

confidence: 99%

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Schlame

Greenberg

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

179

152

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Among mitochondrial lipids, cardiolipin occupies a unique place. It is the only phospholipid that is specific to mitochondria and although it is merely a minor component, accounting for 10–20% of the total phospholipid content, cardiolipin plays an important role in the molecular organization, and thus the function of the cristae. This review covers the formation of cardiolipin, a phospholipid dimer containing two phosphatidyl residues, and its assembly into mitochondrial membranes. While a large body of literature exists on this topic, the review focuses on papers that appeared in the past three years.

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Section: Turnover Of CLmentioning

confidence: 99%

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Schlame

Greenberg

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

179

152

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“…The hydroperoxyl radical, HO 2 ● (i.e., conjugated acid of superoxide) and hydroxyl radical ● OH are capable of initiating non-enzymatic lipid peroxidation, a second line of ROS sources, in which FAs play a pro-oxidant role [ 74 ]. Indeed, hydroperoxyFAs, hydroxyFAs (converted from hydroperoxyFAs by glutathione peroxidase 4, GPX4), and numerous other derivatives of PUFAs coming from enzymatic lipid peroxidation are cleaved from oxidized lipids by phospholipases A2 [ 75 ]. Typically, the shorter lipid peroxidation products (e.g., arachidonic acid metabolites) are pro-inflammatory, while the resolvins coming from the C22 ω-3 PUFAs are anti-inflammatory [ 76 ].…”

Section: Pathology Related To Lcfasmentioning

confidence: 99%

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

et al. 2018

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Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ. Also, excessive dietary FAs stimulate intestine enterocyte incretin secretion, further elevating GSIS, even at low glucose levels, thus contributing to diabetic hyperinsulinemia. With overnutrition and obesity, the FA overload causes impaired GSIS by metabolic dysbalance, paralleled by oxidative and metabolic stress, endoplasmic reticulum stress and numerous pro-apoptotic signaling, all leading to decreased β-cell survival. Lipotoxicity is exerted by saturated FAs, whereas ω-3 polyunsaturated FAs frequently exert antilipotoxic effects. FA-facilitated inflammation upon the recruitment of excess M1 macrophages into islets (over resolving M2 type), amplified by cytokine and chemokine secretion by β-cells, leads to an inevitable failure of pancreatic β-cells.

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“…More recently, in a study examining the effects of lipotoxicity in ␤ -cells, the monolysocardiolipin content was reported to correlate with iPLA 2 ␤ expression level ( 171 ). The authors suggested that iPLA 2 ␤ contributed to cardiolipin remodeling by excising oxidized PUFA residues from cardiolipin to yield monolysocardiolipin species for reacylation with unoxidized C18:2-CoA to regenerate the native cardiolipin structure and function.…”

Section: Proposed Roles For Ipla 2 ␤mentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

169

190

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The Ca 2+ -independent phospholipases A 2 (iPLA 2 s) are part of a diverse family of PLA 2 s that hydrolyze the sn -2 substituent from membrane phospholipids to release a free fatty acid and a lysolipid ( 1, 2 ). These enzymes are ubiquitously expressed, and in contrast to secretory PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s), do not require Ca 2+ for either translocation or activity. Some of the fi rst descriptions of iPLA 2 activity were in the mid-to late-1980s with the identifi cation of a plasmalogen-selective PLA 2 in Abstract Among the family of phospholipases A 2 (PLA 2 s) are the Ca 2+ -independent PLA 2 s (iPLA 2 s) and they are designated group VI iPLA 2 s. In relation to secretory and cytosolic PLA 2 s, the iPLA 2 s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA 2 s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca 2+ for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membraneassociated iPLA 2 ␥ ) and PNPLA9 (cytosol-associated iPLA 2 ␤ ) are the most widely studied and understood. The iPLA 2 s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA 2 s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA 2 s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA 2 s and discussion of the potential mechanisms of action of the iPLA 2 s and related involved lipid mediators. -Ramanadham, S

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Group VIA Phospholipase A2 Mitigates Palmitate-induced β-Cell Mitochondrial Injury and Apoptosis

Cited by 31 publications

References 111 publications

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin

Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

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