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Lithocholic acid delays yeast aging by altering mitochondrial dynamics
Author(s) -
Titorenko Vladimir,
Beach Adam,
Burstein Michelle
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.585.2
Subject(s) - cardiolipin , mitochondrion , mitochondrial fission , mitochondrial fusion , microbiology and biotechnology , biology , phosphatidylethanolamine , inner mitochondrial membrane , reactive oxygen species , biochemistry , chemistry , membrane , mitochondrial dna , phosphatidylcholine , phospholipid , gene
We found that an exogenously added bile acid called lithocholic acid (LCA) delays yeast aging and accumulates in the inner mitochondrial membrane (IMM). To define the mechanism by which LCA extends yeast longevity, we 1) examined how LCA influences mitochondrial proteome and lipidome; 2) investigated the effect of LCA on the composition and stoichiometry of respiratory complexes and supercomplexes in the IMM; 3) assessed how LCA affects mitochondrial oxygen consumption, membrane potential and reactive oxygen species (ROS); 4) examined how LCA influences mitochondrial morphology and how it affects the chronology of events characteristic of age‐related, mitochondria‐controlled apoptosis; and 5) investigated the effect of LCA on the lifespans of long‐ and short‐lived mutants lacking individual components of the mitochondrial fission and fusion machines. Our findings imply that LCA delays yeast aging by increasing the level of phosphatidylserine (PS) and decreasing the levels of phosphatidylethanolamine (PE) and cardiolipin in the IMM. By altering the abundance of these lipid species, LCA greatly expands mitochondrial membrane cristae. In addition, LCA enhances the positive effect of PS and weakens the negative effect of PE on membrane protein machines whose activity they modulate – thereby 1) stimulating protein machines driving mitochondrial respiration, the maintenance of mitochondrial membrane potential and ROS homeostasis, mitochondrial fusion, and protein synthesis in mitochondria; and 2) inhibiting protein machines promoting mitochondrial fission and mitochondria‐controlled apoptosis. Supported by NSERC of Canada.