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首页> 外文期刊>Cell metabolism >Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation.
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Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation.

机译：肝脏中伴侣蛋白介导的自噬不足会导致代谢失调。

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摘要

The activity of chaperone-mediated autophagy (CMA), a catabolic pathway for selective degradation of cytosolic proteins in lysosomes, decreases with age, but the consequences of this functional decline in vivo remain unknown. In this work, we have generated a conditional knockout mouse to selectively block CMA in liver. We have found that blockage of CMA causes hepatic glycogen depletion and hepatosteatosis. The liver phenotype is accompanied by reduced peripheral adiposity, increased energy expenditure, and altered glucose homeostasis. Comparative lysosomal proteomics revealed that key enzymes in carbohydrate and lipid metabolism are normally degraded by CMA and that impairment of their regulated degradation contributes to the metabolic abnormalities observed in CMA-defective animals. These findings highlight the involvement of CMA in regulating hepatic metabolism and suggest that the age-related decline in CMA may have a negative impact on the energetic balance in old organisms.
机译：伴侣介导的自噬（CMA）的活性，一种分解代谢途径，选择性降解溶酶体中的胞质蛋白，随着年龄的增长而降低，但是体内这种功能下降的后果仍然未知。在这项工作中，我们已经产生了条件性基因敲除小鼠，以选择性地阻断肝脏中的CMA。我们发现CMA的阻塞会导致肝糖原耗竭和肝脂肪变性。肝表型伴有周围脂肪减少，能量消耗增加和葡萄糖稳态改变。比较的溶酶体蛋白质组学表明，碳水化合物和脂质代谢中的关键酶通常会被CMA降解，其调节降解的破坏会导致CMA缺陷动物的代谢异常。这些发现凸显了CMA参与调节肝脏代谢，并表明与年龄相关的CMA下降可能对旧生物体的能量平衡产生负面影响。

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