Open AccessMolecular mechanisms underlying genotype‐dependent responses to dietary restriction
Author(s) -
Schleit Jennifer,
Johnson Simon C.,
Bennett Christopher F.,
Simko Marissa,
Trongtham Natalie,
Castanza Anthony,
Hsieh Edward J.,
Moller Richard M.,
Wasko Brian M.,
Delaney Joe R.,
Sutphin George L.,
Carr Daniel,
Murakami Christopher J.,
Tocchi Autumn,
Xian Bo,
Chen Weiyang,
Yu Tao,
Goswami Sarani,
Higgins Sean,
Jeong KiSoo,
Kim Jin R.,
Klum Shan,
Liao Eric,
Lin Michael S.,
Lo Winston,
Miller Hillary,
Olsen Brady,
Peng Zhao J.,
Pollard Tom,
Pradeep Prarthana,
Pruett Dillon,
Rai Dilreet,
Ros Vanessa,
Singh Minnie,
Spector Benjamin L.,
Wende Helen Vander,
An Elroy H.,
Fletcher Marissa,
Jelic Monika,
Rabinovitch Peter S.,
MacCoss Michael J.,
Han JingDong J.,
Kennedy Brian K.,
Kaeberlein Matt
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12130
Subject(s) - biology , proteostasis , prohibitin , genetics , saccharomyces cerevisiae , mitochondrial dna , phenotype , longevity , mitochondrion , genotype , gene , microbiology and biotechnology
Summary Dietary restriction ( DR ) increases lifespan and attenuates age‐related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large‐scale effort to define molecular mechanisms that underlie genotype‐specific responses to DR . The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae . Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar p H homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR . Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mt UPR ), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic m RNA translation. A similar relationship between prohibitins, the mt UPR , and longevity was also observed in C aenorhabditis elegans . These observations define conserved molecular processes that underlie genotype‐dependent effects of DR that may be important modulators of DR in higher organisms.