Loss of Nardilysin, a Mitochondrial Co-chaperone for α-Ketoglutarate Dehydrogenase, Promotes mTORC1 Activation and Neurodegeneration

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• 作者：Wan Hee Yoon¹ ; ² ; Hector Sandoval² ; Sonal Nagarkar-Jaiswal¹ ; ² ; Manish Jaiswal¹ ; ² ; Shinya Yamamoto² ; ³ ; ⁴ ; Nele A. Haelterman³ ; Nagireddy Putluri⁵ ; Vasanta Putluri⁵ ; Arun Sreekumar⁵ ; Tulay Tos⁶ ; Ayse Aksoy⁷ ; Taraka Donti² ; Brett H. Graham² ; ³ ; Mikiko Ohno⁸ ; Eiichiro Nishi⁸ ; Jill Hunter⁹ ; Donna M. Muzny¹⁰ ; Jason Carmichael¹¹ ; Joseph Shen¹¹ ; Valerie A. Arboleda¹² ; Stanley F. Nelson¹² ; Michael F. Wangler² ; ³ ; ⁴ ; Ender Karaca² ; James R. Lupski² ; ¹⁰ ; ¹³ ; Hugo J. Bellen¹ ; ² ; ³ ; ⁴ ; ¹⁴ ; ¹⁵ ; ^{hbellen@bcm.edu}
• 关键词：metabolism ; alpha-ketoglutarate ; mitochondrial chaperones ; TCA cycle ; OGDHL ; NRD1 ; DNAJA3 ; autophagy ; rapamycin
• 刊名：Neuron
• 出版年：2017
• 出版时间：4 January 2017
• 年：2017
• 卷：93
• 期：1
• 页码：115-131
• 全文大小：3656 K
• 卷排序：93

文摘

NRD1 binds to and chaperones OGDH (α-KGDH) in mitochondria Loss of NRD1 or OGDH leads to a progressive neurodegeneration Loss of NRD1 or OGDH increases α-KG, elevates mTORC1 activity, and impairs autophagy Rapamycin alleviates neuronal defects resulting from reduced NRD1 or OGDH function