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By increasing the level of cardiolipin in the inner mitochondrial membrane, a novel anti‐aging small molecule modulates many longevity‐ and disease‐related processes in mitochondria
Author(s) -
Titorenko Vladimir,
Goldberg Alexander,
Bourque Simon,
Beach Adam,
Burstein Michelle,
Richard Vincent,
Kyryakov Pavlo,
Gregg Christopher,
BoukhViner Tatiana,
Juneau Mylène
Publication year - 2010
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.24.1_supplement.474.5
Subject(s) - cardiolipin , mitochondrion , mitochondrial fission , mitochondrial fusion , microbiology and biotechnology , biology , reactive oxygen species , inner mitochondrial membrane , phosphatidylethanolamine , mitophagy , neurodegeneration , saccharomyces cerevisiae , biochemistry , apoptosis , mitochondrial dna , yeast , membrane , autophagy , phospholipid , phosphatidylcholine , medicine , gene , disease
We use the yeast Saccharomyces cerevisiae as a model to study the mechanisms by which age‐related changes in mitochondrial membrane lipids regulate longevity. We identified a novel anti‐aging small molecule, called LA, which increases the concentration of cardiolipin (CL) in the inner mitochondrial membrane. We: 1) assessed the effect of LA on the life spans of long‐ and short‐lived mutants lacking components of the mitochondrial fission, fusion, and tubulation machines or mitochondrial components involved in the biosynthesis of CL and phosphatidylethanolamine (PE); 2) examined how LA influences the chronology of numerous events characteristic of age‐related, mitochondria‐controlled apoptosis; 3) investigated the effect of LA on the susceptibility of yeast to exogenous pro‐apoptotic compounds targeting mitochondria; and 4) assessed the effect of LA on the age‐dependent dynamics of changes in mitochondrial oxygen consumption, membrane potential, and reactive oxygen species (ROS) generation. Our findings imply that: 1) by increasing CL stability and decreasing the “PE/CL” ratio within the mitochondrial membrane, LA specifically reorganizes the protein machines involved in mitochondrial fusion, fission, apoptosis, respiratory chain, and ROS production, thereby delaying aging; and 2) LA can be used for manipulating mitochondrial dysfunction in aging, neurodegeneration and cardiomyopathy.