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SLC25A51是哺乳动物线粒体NAD+转运蛋白
2020-09-12 13:38

美国宾夕法尼亚大学Joseph A. Baur和德克萨斯大学奥斯汀分校Xiaolu A. Cambronne课题组发现,SLC25A51是哺乳动物线粒体烟酰胺腺嘌呤二核苷酸(NAD+)转运蛋白。这一研究成果于2020年9月9日在线发表在国际学术期刊《自然》上。

研究人员发现哺乳动物线粒体能够吸收NAD+,并鉴定了SLC25A51(先前未知功能的必需线粒体蛋白,也称为MCART1)是哺乳动物线粒体NAD+转运蛋白。SLC25A51缺失会降低线粒体NAD+的含量,但不会降低其在全细胞的水平;SLC25A51缺失导致线粒体呼吸作用受损,并阻止NAD+进入分离的线粒体中。

相反,过表达SLC25A51或与其相似的旁系同源物SLC25A52会增加线粒体NAD+含量,并使NAD+进入到缺乏内源NAD+转运蛋白的酵母线粒体中。总之,该研究揭示了SLC25A51是第一个介导NAD+进入哺乳动物线粒体的转运蛋白。

据了解,线粒体需要NAD+来执行呼吸产能和介导细胞能量转运的基本功能。已在酵母和植物中鉴定了线粒体NAD+转运蛋白,但它们是否也存在于哺乳动物中仍有争议。

附:英文原文

Title: SLC25A51 is a mammalian mitochondrial NAD + transporter

Author: Timothy S. Luongo, Jared M. Eller, Mu-Jie Lu, Marc Niere, Fabio Raith, Caroline Perry, Marc R. Bornstein, Paul Oliphint, Lin Wang, Melanie R. McReynolds, Marie E. Migaud, Joshua D. Rabinowitz, F. Brad Johnson, Kai Johnsson, Mathias Ziegler, Xiaolu A. Cambronne, Joseph A. Baur

Issue&Volume: 2020-09-09

Abstract: Mitochondria require nicotinamide adenine dinucleotide (NAD+) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD+ transporters have been identified in yeast and plants1,2 but their very existence is controversial in mammals3–5. Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD+ and identify SLC25A51 (an essential6,7 mitochondrial protein of previously unknown function, also known as MCART1) as a mammalian mitochondrial NAD+ transporter. Loss of SLC25A51 decreases mitochondrial but not whole-cell NAD+ content, impairs mitochondrial respiration, and blocks the uptake of NAD+ into isolated mitochondria. Conversely, overexpression of SLC25A51 or a nearly identical paralog, SLC25A52, increases mitochondrial NAD+ levels and restores NAD+ uptake into yeast mitochondria lacking endogenous NAD+ transporters. Together, these findings identify SLC25A51 as the first transporter capable of importing NAD+ into mammalian mitochondria.

DOI: 10.1038/s41586-020-2741-7

Source: https://www.nature.com/articles/s41586-020-2741-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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