title: Calorie restriction promotes cardiolipin biosynthesis and distribution between mitochondrial membranes.
abstract: Calorie restriction (CR) has been amply demonstrated to modify mitochondrial function. However, little is known regarding the effects of this dietary regimen on mitochondrial membranes. We isolated phospholipids from rat liver mitochondria from animals on CR or ad libitum diets and found that mitochondria from ad libitum animals present an increased content of lipoperoxides and the content of cardiolipin. Cardiolipin is the main anionic phospholipid present in mitochondrial membranes, and plays a key role in mitochondrial function, signaling and stress response. Expression levels of the enzymes involved in cardiolipin biosynthesis and remodeling were quantified and found to be upregulated in CR animals. Interestingly, when mitochondrial membranes were fractionated, the outer membrane presented a higher content of cardiolipin, indicating a redistribution of this phospholipid mediated by a phospholipid scramblase in CR. This change is associated with Drp1-mediated mitochondrial fragmentation and autophagy. Overall, we find that CR promotes extensive mitochondrial membrane remodeling, decreasing oxidatively damaged lipids, and increasing cardiolipin levels and redistributing cardiolipin. These changes in membrane properties are consistent with and may be causative of changes in mitochondrial morphology, function and turnover previously found to occur in CR.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil. Electronic address: aluevano@iq.usp.br.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Luévano-Martínez
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil.
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Forni
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil.
authors.forename: Julia
authors.initials: J
authors.lastname: Peloggia
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Ii-Sei
authors.initials: IS
authors.lastname: Watanabe
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brazil.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D000818:Animals; D001343:Autophagy; D031204:Caloric Restriction; D002308:Cardiolipins / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002308:Cardiolipins; C519851:Dnm1l protein, rat; D034281:Dynamins
keywords: Calorie restriction; Cardiolipin; Membrane; Mitochondria; Phospholipid