Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.
Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.
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饮食限制和AMPK通过线粒体网络和过氧化物酶体重塑增加寿命。
DOI：
10.1016/j.cmet.2017.09.024
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发表时间：
2017-12-05
期刊：
影响因子：
29
通讯作者：
Mair WB
中科院分区：
文献类型：
--
作者：
Weir HJ;Yao P;Huynh FK;Escoubas CC;Goncalves RL;Burkewitz K;Laboy R;Hirschey MD;Mair WB
Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity in C. elegans via maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity. Finally, we show that increasing lifespan via maintaining mitochondrial network homeostasis requires FAO and peroxisomal function. Together these data demonstrate that mechanisms that promote mitochondrial homeostasis and plasticity can be targeted to promote healthy aging. Dysfunctional mitochondrial dynamics are a hallmark of aging, but the physiological consequences are unknown. Weir et al. show that mitochondrial network remodeling is required for AMPK- and dietary restriction-mediated longevity, and identify a downstream role for fatty acid oxidation and peroxisome function in C. elegans.
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