The influence of the acyl chain composition of cardiolipin on the stability of mitochondrial complexes; an unexpected effect of cardiolipin in alpha-ketoglutarate dehydrogenase and prohibitin complexes.
The role of cardiolipin acyl chain composition in assembly/stabilization of mitochondrial complexes was investigated using three yeast deletion mutants (acb1Delta strain; taz1Delta strain; and acb1Deltataz1Delta strain). Deletion of the TAZ1 gene, involved in cardiolipin acyl chain remodeling, is known to increase the content of monolyso-cardiolipin (MLCL) at the expense of CL, and to decrease the unsaturation of the remaining CL. Deletion of the ACB1 gene encoding the acyl-CoA-binding protein, involved in fatty acid elongation, decreases the average length of the CL acyl chains. Furthermore, a TAZ1ACB1 double deletion mutant strain was used in this study which has both a decrease in the length of the CL acyl chains and an increase in MLCL. BN/SDS PAGE analysis revealed that cardiolipin is important for the prohibitin-m-AAA protease complex, the alpha-ketoglutarate dehydrogenase complex and respiratory chain supercomplexes. The results indicate that the decreased level of complexes in taz1Delta and acb1Deltataz1Delta mitochondria is due to a decreased content of CL or the presence of MLCL.
van Gestel
Renske A
RA
Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Rijken
Pieter J
PJ
Surinova
Silvia
S
O'Flaherty
Martina
M
Heck
Albert J R
AJ
Killian
J Antoinette
JA
de Kroon
Anton I P M
AI
Slijper
Monique
M
D000215:Acylation; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism*; D002853:Chromatography, Liquid; D026261:Diazepam Binding Inhibitor / Q000737:chemistry / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D017353:Gene Deletion; D007655:Ketoglutarate Dehydrogenase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D008666:Metalloendopeptidases / Q000378:metabolism; D008928:Mitochondria / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D000091402:Prohibitins; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
D002308:Cardiolipins; D026261:Diazepam Binding Inhibitor; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D000091402:Prohibitins; D012097:Repressor Proteins; D007655:Ketoglutarate Dehydrogenase Complex; D008666:Metalloendopeptidases; C114583:m-AAA proteases