FB2025_01 , released February 20, 2025
Reference Report
Open Close
Reference
Citation
Ren, M., Xu, Y., Phoon, C.K.L., Erdjument-Bromage, H., Neubert, T.A., Schlame, M. (2023). Cardiolipin prolongs the lifetimes of respiratory proteins in Drosophila flight muscle.  J. Biol. Chem. 299(10): 105241.
FlyBase ID
FBrf0257881
Publication Type
Research paper
Abstract
Respiratory complexes and cardiolipins have exceptionally long lifetimes. The fact that they co-localize in mitochondrial cristae raises the question of whether their longevities have a common cause and whether the longevity of OXPHOS proteins is dependent on cardiolipin. To address these questions, we developed a method to measure side-by-side the half-lives of proteins and lipids in wild-type Drosophila and cardiolipin-deficient mutants. We fed adult flies with stable isotope-labeled precursors ([13]C6[15]N2-lysine or [13]C6-glucose) and determined the relative abundance of heavy isotopomers in protein and lipid species by mass spectrometry. To minimize the confounding effects of tissue regeneration, we restricted our analysis to the thorax, the bulk of which consists of post-mitotic flight muscles. Analysis of 680 protein and 45 lipid species showed that the subunits of respiratory complexes I-V and the carriers for phosphate and ADP/ATP were among the longest-lived proteins (average half-life of 48 ± 16 days) while the molecular species of cardiolipin were the longest-lived lipids (average half-life of 27 ± 6 days). The remarkable longevity of these crista residents was not shared by all mitochondrial proteins, especially not by those residing in the matrix and the inner boundary membrane. Ablation of cardiolipin synthase, which causes replacement of cardiolipin by phosphatidylglycerol, and ablation of tafazzin, which causes partial replacement of cardiolipin by monolyso-cardiolipin, decreased the lifetimes of the respiratory complexes. Ablation of tafazzin also decreased the lifetimes of the remaining cardiolipin species. These data suggest that an important function of cardiolipin in mitochondria is to protect respiratory complexes from degradation.
PubMed ID
PubMed Central ID
PMC10622840 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Biol. Chem.
    Title
    Journal of Biological Chemistry
    Publication Year
    1905-
    ISBN/ISSN
    0021-9258
    Data From Reference