智利CECs科学研究中心L. Felipe Barros小组宣布他们研制了线粒体乳酸释放限制氧化应激。2026年3月24日出版的《细胞—代谢》发表了这项成果。

通过在体内培养细胞和神经元中使用遗传编码的乳酸和氧化还原传感器，该团队在线粒体基质中发现了一个动态乳酸池，它可以跟踪细胞外和血液中的乳酸，并促进线粒体蛋白的乳酸化。乳酸通过饱和途径穿过线粒体内膜，该途径对线粒体丙酮酸载体（MPC）的药理学和遗传抑制部分敏感。尽管有传输和基质乳酸脱氢酶活性，但在测试条件下，乳酸不能测量电子传递链的能量。相反，充满能量的线粒体可以从丙酮酸中产生乳酸，这种反应在缺氧的情况下得到加强。阻断MPC羧糖基质乳酸和HO积累，揭示了一个快速的乳酸“喷口”，调节基质能量和活性氧。

据介绍，乳酸被提出进入线粒体并为呼吸提供燃料，但这种“细胞内乳酸穿梭”仍然存在争议。

附：英文原文

Title: Mitochondrial lactate venting limits oxidative stress

Author: Daniela Rauseo, Yasna Contreras-Baeza, Mildreth Salazar, Abigail J. Galarza, Sebastián Holtheuer-Gallardo, Hugo Faurand, Natali Cárcamo-Lemus, Raibel Suárez, Joel L. Asenjo, Alexandra von Faber-Castell, Franco Silva, Valentina Mora-González, Jan Dernic, Luca Ravotto, Matthias T. Wyss, Felipe Baeza-Lehnert, Iván Ruminot, Carlos Alvarez-Navarro, Alejandro San Martín, Bruno Weber, Pamela Y. Sandoval, L. Felipe Barros

Issue&Volume: 2026-03-24

Abstract: Lactate has been proposed to enter mitochondria and fuel respiration, but this “intracellular lactate shuttle” remains controversial. Using genetically encoded lactate and redox sensors in cultured cells and neurons in vivo, we identify a dynamic lactate pool within the mitochondrial matrix that tracks extracellular and blood lactate and promotes lactylation of mitochondrial proteins. Lactate crosses the inner mitochondrial membrane through a saturable pathway that is partly sensitive to pharmacologic and genetic inhibition of the mitochondrial pyruvate carrier (MPC). Despite transport and matrix lactate dehydrogenase activity, lactate does not measurably energize the electron transport chain under the conditions tested. Instead, energized mitochondria can produce lactate from pyruvate, a response enhanced by hypoxia. Blocking MPC causes matrix lactate and HO accumulation, revealing a rapid lactate-based “vent” that modulates matrix energy and reactive oxygen species.

DOI: 10.1016/j.cmet.2026.02.020

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(26)00093-8