2.7.8.41	evolution	CL synthase (CLS) with two phospholipase D domains, i.e. CLS_pld, and CLS with one CDP-alcohol phosphatidyltransferase domain, i.e. CLS_cap, function in bacteria and eukaryotes (mitochondria), respectively. Phylogenetic analysis, overview. Exceptions to the above-mentioned hypothesis regarding CLS phylogenetic distribution, in which CLS_pld and CLS_cap are exclusively found in bacteria and eukaryotes, respectively, are found in actinobacteria and proteobacteria, that contain CLS_cap-like proteins. The eukaryotic supergroups Amoebozoa, Excavata, and Alveolata, a subgroup of the supergroup SAR, have only CLS_pld (without phylogenetic affiliation to any particular bacterial homologues), while the supergroups Opisthokonta (including animals and fungi) and Archaeplastida (including land plants) along with another SAR subgroup stramenopiles possess only CLS_cap (closely related to alpha-proteobacterial homologues). Cafeteria roenbergensis contains only a CLS_cap enzyme homologue, no CLS_pld homologue	-, 739118	
2.7.8.41	evolution	CL synthase (CLS) with two phospholipase D domains, i.e. CLS_pld, and CLS with one CDP-alcohol phosphatidyltransferase domain, i.e. CLS_cap, function in bacteria and eukaryotes (mitochondria), respectively. Phylogenetic analysis, overview. Exceptions to the above-mentioned hypothesis regarding CLS phylogenetic distribution, in which CLS_pld and CLS_cap are exclusively found in bacteria and eukaryotes, respectively, are found in actinobacteria and proteobacteria, that contain CLS_cap-like proteins. The eukaryotic supergroups Amoebozoa, Excavata, and Alveolata, a subgroup of the supergroup SAR, have only CLS_pld (without phylogenetic affiliation to any particular bacterial homologues), while the supergroups Opisthokonta (including animals and fungi) and Archaeplastida (including land plants) along with another SAR subgroup stramenopiles possess only CLS_cap (closely related to alpha-proteobacterial homologues). Cafeteria sp. Caron contains both, a CLS_cap enzyme homologue, and a CLS_pld homologue	739118	
2.7.8.41	evolution	CL synthase (CLS) with two phospholipase D domains, i.e. CLS_pld, and CLS with one CDP-alcohol phosphatidyltransferase domain, i.e. CLS_cap, function in bacteria and eukaryotes (mitochondria), respectively. Phylogenetic analysis, overview. Exceptions to the above-mentioned hypothesis regarding CLS phylogenetic distribution, in which CLS_pld and CLS_cap are exclusively found in bacteria and eukaryotes, respectively, are found in actinobacteria and proteobacteria, that contain CLS_cap-like proteins. The eukaryotic supergroups Amoebozoa, Excavata, and Alveolata, a subgroup of the supergroup SAR, have only CLS_pld (without phylogenetic affiliation to any particular bacterial homologues), while the supergroups Opisthokonta (including animals and fungi) and Archaeplastida (including land plants) along with another SAR subgroup stramenopiles possess only CLS_cap (closely related to alpha-proteobacterial homologues). Developayella elegans contains only a CLS_cap enzyme homologue, no CLS_pld homologue	-, 739118	
2.7.8.41	evolution	CL synthase (CLS) with two phospholipase D domains, i.e. CLS_pld, and CLS with one CDP-alcohol phosphatidyltransferase domain, i.e. CLS_cap, function in bacteria and eukaryotes (mitochondria), respectively. Phylogenetic analysis, overview. Exceptions to the above-mentioned hypothesis regarding CLS phylogenetic distribution, in which CLS_pld and CLS_cap are exclusively found in bacteria and eukaryotes, respectively, are found in actinobacteria and proteobacteria, that contain CLS_cap-like proteins. The eukaryotic supergroups Amoebozoa, Excavata, and Alveolata, a subgroup of the supergroup SAR, have only CLS_pld (without phylogenetic affiliation to any particular bacterial homologues), while the supergroups Opisthokonta (including animals and fungi) and Archaeplastida (including land plants) along with another SAR subgroup stramenopiles possess only CLS_cap (closely related to alpha-proteobacterial homologues). Wobblia lunata contains both, a CLS_cap enzyme homologue, and a CLS_pld homologue	-, 739118	
2.7.8.41	evolution	phosphatidylglycerophosphate synthase (PGPS) and cardiolipin synthase (CLS) are both involved in the biosynthesis of phosphatidylglycerol and cardiolipin and belong to the CDP-alcohol phosphotransferases, they share overall amino acid sequence homology. PGPS and CLS are functionally distinct in vivo. Comparison of CDP-alcohol phosphotransferase motifs between PGPS and CLS among different species reveal a possible additional motif that might define the substrate specificity of the closely related enzymes	-, 738289	
2.7.8.41	malfunction	a yeast mutant with a deletion of YDL142c is defective in the formation of cardiolipin. A cls1 deletion strain is viable on glucose, galactose, ethanol, glycerol and lactate containing media, although the growth rate on nonfermentable carbon sources is decreased. Mitochondria of the cls1 mutant are devoid of cardiolipin but accumulate the cardiolipin precursor phosphatidylglycerol when grown on nonfermentable carbon sources	-, 727498	
2.7.8.41	malfunction	in contrast to yeast, where development of deletion mutants is little affected, the Arabidopsis seedlings are slow developing under short-day conditions in vitro and die if they are transferred to long-day conditions	728476	
2.7.8.41	malfunction	null mutant can grow on both fermentable and non-fermentable carbon sources at lower temperatures, it cannot form colonies at 37°C	-, 728313	
2.7.8.41	malfunction	overexpression of clsA results in weakened hyphal tips, misshaped aerial hyphae and anucleate spores and demonstrates that cardiolipin synthesis is a requirement for morphogenesis in Streptomyces	-, 728326	
2.7.8.41	metabolism	cardiolipin is known to be biosynthesized by either of two phylogenetically distinct enzymes: CL synthase (CLS) with two phospholipase D domains, i.e. CLS_pld, which synthesizes cardiolipin from two molecules of phosphatidylglycerols or CLS with one CDP-alcohol phosphatidyltransferase domain, i.e. CLS_cap, which produces this lipid using a phosphatidylglycerol and a cytidine diphosphate diacylglycerol as substrates. In contrast to the bacterial-type CL, mitochondrial immature cardiolipin synthesized by CLS is further remodeled (reacylated), resulting in mature cardiolipin generally possessing the same fatty acids at sn-1, 2 sites in one molecule. This eukaryotic cardiolipin maturation pathway consists of two steps: in the first step, immature ardiolipin is deacylated into monolysocardiolipin (MLCL) with either cardiolipin-specific phospholipase (CLD) or calcium-independent phospholipase A2 (iPLA2) beta/gamma	-, 739118	
2.7.8.41	metabolism	cardiolipin is known to be biosynthesized by either of two phylogenetically distinct enzymes: CL synthase (CLS) with two phospholipase D domains, i.e. CLS_pld, which synthesizes cardiolipin from two molecules of phosphatidylglycerols or CLS with one CDP-alcohol phosphatidyltransferase domain, i.e. CLS_cap, which produces this lipid using a phosphatidylglycerol and a cytidine diphosphate diacylglycerol as substrates. In contrast to the bacterial-type CL, mitochondrial immature cardiolipin synthesized by CLS is further remodeled (reacylated), resulting in mature cardiolipin generally possessing the same fatty acids at sn-1, 2 sites in one molecule. This eukaryotic cardiolipin maturation pathway consists of two steps: in the first step, immature cardiolipin is deacylated into monolysocardiolipin (MLCL) with either cardiolipin-specific phospholipase (CLD) or calcium-independent phospholipase A2 (iPLA2) beta/gamma	-, 739118	
2.7.8.41	metabolism	cardiolipin synthase in liver mitochondria increases significantly in rats treated with thyroxine. Control cardiolipin synthase activity is 22.4 pmol/mg*h versus 34.1 pmol/mg*h in thyroxine-treated liver mitochondria	727056	
2.7.8.41	metabolism	cardiolipin synthase is involved in the biosynthesis of cardiolipin	-, 738289	
2.7.8.41	physiological function	cardiolipin synthase is involved in maintaining physiologic membrane structure and function even under metabolic stress	727909	
2.7.8.41	physiological function	cardiolipin synthesis is a requirement for morphogenesis in Streptomyces	-, 728326	
2.7.8.41	physiological function	expression of CLS complements cardiolipin production in CRD1 knockout Saccharomyces cerevisiae and partly restores wild-type colony forming capability under stress conditions. Cardiolipin remodeling appears to be impaired in the transgenic construct. No complementation is observed by heterologous expression of Saccharomyces cerevisiae Crd1 in conditional CLS knockout trypanosomes, despite proper mitochondrial targeting of the protein	761829	
2.7.8.41	physiological function	expression of CRD1 is essential for normal colony formation at elevated temperatures	-, 728313	
2.7.8.41	physiological function	expression of Trypanosoma brucei CLS complements cardiolipin production in CRD1 knockout Saccharomyces cerevisiae and partly restores wild-type colony forming capability under stress conditions. Cardiolipin remodeling appears to be impaired in the transgenic construct. No complementation is observed by heterologous expression of Crd1 in conditional CLS knockout trypanosomes, despite proper mitochondrial targeting of the protein	761829	
2.7.8.41	physiological function	gene CrCLS1 does not complement the growth phenotype of a phosphatidylglycerophosphate synthase (PGPS) mutant of Synechocystis sp. PCC6803, but it rescues the temperature-sensitive growth phenotype, growth profile with different carbon sources, phospholipid composition, and enzyme activity of DELTAcrd1, a cardiolipin synthase (CLS) mutant of Saccharomyces cerevisiae	-, 738289	
2.7.8.41	physiological function	knockdown of cardiolipin synthase induces mitochondrial elongation in body wall muscle cells. Knockdown of other genes involved in cardiolipin synthesis does not influence mitochondrial morphology. Knocking down cardiolipin synthase decreases mitochondrial division	761083	
2.7.8.41	physiological function	knockdown of cardiolipin synthase induces mitochondrial elongation in human cells. In cardiolipin synthase-knocked down cells a decreased amount of cardiolipin and an accumulation of phosphatidylglycerol is observed. Knockdown of other genes involved in cardiolipin synthesis does not influence mitochondrial morphology	761083	
2.7.8.41	physiological function	overexpression of Crls1 markedly attenuates hepatic steatosis and inflammation in hepatocytes, whereas shRNA-mediated Crls1 knockdown aggravates these abnormalities. High-fat diet-induced insulin resistance and hepatic steatosis are significantly exacerbated in hepatocyte-specific Crls1-knockout mice. Crls1 depletion significantly aggravates high-fat and high-cholesterol diet-induced inflammatory response and fibrosis during nonalcoholic hepatic steatosis development. Crls1 deficiency leads to a prominently aggravated lipid metabolism disorder. Activating transcription factor 3 (ATF3) is the key differentially expressed gene in Crls1-knockout mice	761225	
2.7.8.41	physiological function	phosphatidylglycerophosphate synthase PGS1 and CLS1 are constituents of large protein complexes. PGS1 forms oligomers and associates with CLS1 and phosphatidylglycerophosphate phosphatase PTPMT1. Cardiolipin and CLS1 are not required for PGS1 to assemble in the complex. PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS components MIC60 and MIC19	760627	
2.7.8.41	physiological function	synthesis of cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Overexpression of cardiolipin synthase Crls1 enhances energy consumption in adipocytes, and adipose Crls1 levels positively correlate with insulin sensitivity	760835	
2.7.8.41	physiological function	synthesis of cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Overexpression of cardiolipin synthase Crls1 enhances energy consumption in adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant	760835	
2.7.8.41	physiological function	the enzyme catalyzes the terminal step in cardiolipin biosynthesis. Cardiolipin is essential for mitochondrial structure and function	728087	
2.7.8.41	physiological function	the enzyme is crucial for correct mitochondrial function and development in Arabidopsis under both optimal and stress conditions	728476