A Mitochondrial ATP Synthase Subunit Interacts with TOR Signaling to Modulate Protein Homeostasis and Lifespan in Drosophila

Autor: Xiaoping Sun, Charles T. Wheeler, Jason Yolitz, Mara Laslo, Thomas Alberico, Yaning Sun, Qisheng Song, Sige Zou
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Cell Reports, Vol 8, Iss 6, Pp 1781-1792 (2014)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2014.08.022
Popis: Diet composition is a critical determinant of lifespan, and nutrient imbalance is detrimental to health. However, how nutrients interact with genetic factors to modulate lifespan remains elusive. We investigated how diet composition influences mitochondrial ATP synthase subunit d (ATPsyn-d) in modulating lifespan in Drosophila. ATPsyn-d knockdown extended lifespan in females fed low carbohydrate-to-protein (C:P) diets but not the high C:P ratio diet. This extension was associated with increased resistance to oxidative stress; transcriptional changes in metabolism, proteostasis, and immune genes; reduced protein damage and aggregation, and reduced phosphorylation of S6K and ERK in TOR and mitogen-activated protein kinase (MAPK) signaling, respectively. ATPsyn-d knockdown did not extend lifespan in females with reduced TOR signaling induced genetically by Tsc2 overexpression or pharmacologically by rapamycin. Our data reveal a link among diet, mitochondria, and MAPK and TOR signaling in aging and stresses the importance of considering genetic background and diet composition in implementing interventions for promoting healthy aging.
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