Loss of Cardiolipin Leads to Longevity Defects That Are Alleviated by Alterations in Stress Response Signaling*

AUTOR(ES)

Zhou, Jingming

FONTE

American Society for Biochemistry and Molecular Biology

RESUMO

Perturbation of cardiolipin (CL) synthesis in yeast cells leads to defective respiratory chain function and mitochondrial DNA loss, both of which have been implicated in aging in mammals. The availability of yeast CL mutants enabled us to directly investigate the role of CL synthesis in aging. In this report, we show that the replicative life span of pgs1Δ, which lacks both CL and the precursor phosphatidylglycerol (PG), was significantly decreased at 30 °C. The life span of crd1Δ, which has PG but not CL, was unaffected at 30 °C but reduced at 37 °C. Life span extension induced by calorie restriction was not affected by the loss of CL. However, mild heat and osmotic stress, which extend life span in wild type cells, did not increase longevity in CL mutants, suggesting that the stress response is perturbed in these mutants. Consistent with this, longevity defects in pgs1Δ were alleviated by down-regulation of the high osmolarity glycerol stress response pathway, as well as by promoting cell integrity with the osmotic stabilizer sorbitol or via genetic suppression with the kre5W1166X mutant. These findings show for the first time that perturbation of CL synthesis leads to decreased longevity in yeast, which is restored by altering signaling through stress response pathways.

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