Double bonds of unsaturated fatty acids differentially regulate mitochondrial cardiolipin remodeling

Ting, Hsiu-Chi; Chen, Li-Tzu; Chen, Jo-Yu; Huang, Yi-Li; Xin, Rui-Cheng; Chan, Jui-Fen; Hsu, Yuan-Hao

doi:10.1186/s12944-019-0990-y

Cited by 23 publications

(24 citation statements)

References 43 publications

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“…GO and KEGG analyses confirmed the involvement of FADS1 in fatty acid metabolism, including long-chain fatty acid metabolic processing, which is essential for functional activity in mitochondria [18]. In addition, PUFA could regulate mitochondrial membrane structure and function [19]. Previous study indicated that there are significant differences in the mitochondrial morphology of vitiligo skin compared with that in health skin [20].…”

Section: Discussionmentioning

confidence: 76%

Suppression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanocytes: implications for vitiligo

Tang

et al. 2019

Aging

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Vitiligo is a potentially serious condition characterized by loss of melanin and death of melanocytes. To identify potential therapeutic targets for vitiligo, we conducted a microarray analysis of three human vitiligo specimens and paired adjacent normal tissues. Because we found that the fatty acid desaturase 1 (FADS1) gene was downregulated in vitiligo specimens, we carried out experiments to assess its role in melanocyte replication and survival. RT-qPCR was used to verify that FADS1 expression was lower in vitiligo-affected tissues and vitiligo melanocyte PIG3V cells than in matched controls or normal human epidermal PIG1 melanocytes. In addition, CCK-8, immunofluorescence, western blot and flow cytometry assay were used to detect the proliferation and apoptosis in PIG1 cells respectively. Overexpression of FADS1 promoted proliferation of PIG3V melanocytes, while FADS1 silencing inhibited proliferation and induced cell death in PIG1 melanocytes. Increased ROS generation; induction of mitochondrial-mediated apoptosis via upregulation of Bax and active caspases 3 and 9 and downregulation of Bcl-2; and cell cycle arrest via downregulation of c-Myc and Cyclin D1 and upregulation of p21 were all enhanced after FADS1 silencing in PIG1 melanocytes. These findings implicate FADS1 downregulation in the pathogenesis of vitiligo and may open new avenues for its treatment.

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Section: Discussionmentioning

confidence: 76%

Suppression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanocytes: implications for vitiligo

Tang

et al. 2019

Aging

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“…Our present data are limited to model experiments that must have confirmation for their application to biological systems. Two scenarios relevant for our data can be depicted: (i) the presence of H 2 S, at remarkable concentrations after its enzymatic production in mitochondria [ 55 , 56 ], and the isomerizing ability of its small diffusible radicals, such as HS • or the deprotonated form S •− [ 57 ], suggesting to monitor mitochondria with in vitro and in vivo experiments; (ii) the CL oxidation and the effects of several protective agents, monitored by the increase in CL contents [ 24 ], indicating the importance of a follow-up of CL isomerization under various stress conditions, in order to individuate antioxidants able to also preserve the natural cis double bond geometry [ 28 ]. The need for a multidisciplinary approach in the study of this interesting biomolecule clearly emerges.…”

Section: Discussionmentioning

confidence: 99%

“…The analytical aspect concerning the identification of trans CL isomers is a crucial issue to address, with the specific goal to have protocols that can examine biological specimens. At present, CL analysis includes: (i) the isolation of CL via preparative thin layer chromatography (TLC) and transesterification to obtain the corresponding fatty acid methyl esters (FAME) under acidic conditions (HCl, H 2 SO 4 or BF 3 in methanol) to proceed with the gas chromatographic (GC) identification of the fatty acid residues [ 21 , 22 , 23 , 24 ]; (ii) HPLC with tandem MS/MS analysis to identify cardiolipins among other lipid classes [ 25 , 26 , 27 , 28 , 29 ]. Based on our experience in fatty acid-based lipidomics [ 2 , 19 ], the transesterification conditions must ensure a quantitative performance and the analytical conditions need to separate and identify cis and trans isomers.…”

Section: Introductionmentioning

confidence: 99%

Free-Radical-Mediated Formation of Trans-Cardiolipin Isomers, Analytical Approaches for Lipidomics and Consequences of the Structural Organization of Membranes

et al. 2020

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Free-radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions, have a trans-disciplinary relevance. Cardiolipins (CL, (1,3-diphosphatidyl-sn-glycerol)) and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipids, where they maintain membrane integrity and regulate enzyme functionalities. Peroxidation pathways and fatty acid remodeling are known causes of mitochondrial disfunctions and pathologies, including cancer. Free-radical-mediated isomerization with the change of the cis CL into geometrical trans isomers is an unknown process with possible consequences on the supramolecular membrane lipid organization. Here, the formation of mono-trans CL (MT-CL) and other trans CL isomers (T-CL) is reported using CL from bovine heart mitochondria and thiyl radicals generated by UV-photolysis from 2-mercaptoethanol. Analytical approaches for CL isomer separation and identification via 1H/13C NMR are provided, together with the chemical study of CL derivatization to fatty acid methyl esters (FAME), useful for lipidomics and metabolomics research. Kinetics information of the radical chain isomerization process was obtained using γ-irradiation conditions. The CL isomerization affected the structural organization of membranes, as tested by the reduction in unilamellar liposome diameter, and accompanied the well-known process of oxidative consumption induced by Fenton reagents. These results highlight a potential new molecular modification pathway of mitochondrial lipids with wide applications to membrane functions and biological consequences.

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“…Cardiolipin can interact with the respiratory chain complexes and contribute to generate the electrochemical gradient. Additionally, since it can interact with death-inducing proteins, it is involved in the apoptotic process and oxidation of cardiolipin compromises apoptosis, promoting neuronal dysfunctions and the progression of neurodegeneration (e.g., Alzheimer's and Parkinson's disease) [80,81]. Coherently with this picture, plenty of studies highlight the involvement of mitochondrial dysfunctions in neurodegeneration [3,[82][83][84], supporting the relevance of protecting systems, including antioxidant defenses, to maintain neuronal integrity and survival [85].…”

Section: Mitochondria In Neurodegeneration: the Interplay Between Oximentioning

confidence: 96%

“…Moreover, ROS control the expression of highly conserved heat-shock proteins, and the increased mitochondrial ROS production can perturb the folding of proteins synthesized by mitochondria [79]. Finally, oxidation of cardiolipin's acyl chains at the mitochondrial inner membrane can cause respiratory complex destabilization [79,80]. Cardiolipin can interact with the respiratory chain complexes and contribute to generate the electrochemical gradient.…”

Section: Mitochondria In Neurodegeneration: the Interplay Between Oximentioning

confidence: 99%

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

Bordoni

Gabbianelli

2020

Antioxidants

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The maintenance of the mitochondrial function is essential in preventing and counteracting neurodegeneration. In particular, mitochondria of neuronal cells play a pivotal role in sustaining the high energetic metabolism of these cells and are especially prone to oxidative damage. Since overproduction of reactive oxygen species (ROS) is involved in the pathogenesis of neurodegeneration, dietary antioxidants have been suggested to counteract the detrimental effects of ROS and to preserve the mitochondrial function, thus slowing the progression and limiting the extent of neuronal cell loss in neurodegenerative disorders. In addition to their role in the redox-system homeostasis, mitochondria are unique organelles in that they contain their own genome (mtDNA), which acts at the interface between environmental exposures and the molecular triggers of neurodegeneration. Indeed, it has been demonstrated that mtDNA (including both genetics and, from recent evidence, epigenetics) might play relevant roles in modulating the risk for neurodegenerative disorders. This mini-review describes the link between the mitochondrial genome and cellular oxidative status, with a particular focus on neurodegeneration; moreover, it provides an overview on potential beneficial effects of antioxidants in preserving mitochondrial functions through the protection of mtDNA.

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Double bonds of unsaturated fatty acids differentially regulate mitochondrial cardiolipin remodeling

Cited by 23 publications

References 43 publications

Suppression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanocytes: implications for vitiligo

Suppression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanocytes: implications for vitiligo

Free-Radical-Mediated Formation of Trans-Cardiolipin Isomers, Analytical Approaches for Lipidomics and Consequences of the Structural Organization of Membranes

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

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