美国布莱根妇女医院和哈佛医学院Victor W. Hsu团队在研究中取得进展。他们研究出ALDH7A1通过产生膜NADH和调节FSP1来防止铁下垂。2025年4月14日，国际知名学术期刊《细胞》发表了这一成果。

该课题组最初发现NADH在细胞膜上存在显著水平，然后发现这种形式的NADH是由醛脱氢酶7A1 （ALDH7A1）产生的，以支持FSP1活性。ALDH7A1活性也通过消耗活性醛直接减少脂质过氧化。

此外，ALDH7A1促进了FSP1的膜募集，这是由铁致应力激活AMP活化蛋白激酶（AMPK）引起的，从而促进了ALDH7A1的膜定位，从而稳定了膜上的FSP1。这些发现通过揭示细胞膜上以前未被发现的NADH池，促进了对NADH的基本理解，阐明了其功能，提供了对FSP1如何起作用以及醛脱氢酶如何防止铁凋亡的主要理解。

据悉，铁下垂是一种由铁诱导的脂质过氧化引起的细胞死亡。铁凋亡抑制蛋白1（FSP1）通过产生抗氧化剂来防止这种死亡，这需要烟酰胺腺嘌呤二核苷酸还原形式（NADH）作为辅助因子。

附：英文原文

Title: ALDH7A1 protects against ferroptosis by generating membrane NADH and regulating FSP1

Author: Jia-Shu Yang, Andrew J. Morris, Koki Kamizaki, Jianzhong Chen, Jillian Stark, William M. Oldham, Toshitaka Nakamura, Eikan Mishima, Joseph Loscalzo, Yasuhiro Minami, Marcus Conrad, Whitney S. Henry, Victor W. Hsu

Issue&Volume: 2025-04-14

Abstract: Ferroptosis is a form of cell death due to iron-induced lipid peroxidation. Ferroptosis suppressor protein 1 (FSP1) protects against this death by generating antioxidants, which requires nicotinamide adenine dinucleotide, reduced form (NADH) as a cofactor. We initially uncover that NADH exists at significant levels on cellular membranes and then find that this form of NADH is generated by aldehyde dehydrogenase 7A1 (ALDH7A1) to support FSP1 activity. ALDH7A1 activity also acts directly to decrease lipid peroxidation by consuming reactive aldehydes. Furthermore, ALDH7A1 promotes the membrane recruitment of FSP1, which is instigated by ferroptotic stress activating AMP-activated protein kinase (AMPK) to promote the membrane localization of ALDH7A1 that stabilizes FSP1 on membranes. These findings advance a fundamental understanding of NADH by revealing a previously unappreciated pool on cellular membranes, with the elucidation of its function providing a major understanding of how FSP1 acts and how an aldehyde dehydrogenase protects against ferroptosis.

DOI: 10.1016/j.cell.2025.03.019

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00292-2