Mitochondria acidify lysosomes through membrane contacts

Cell Reports 2026 Open access

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Authors: Zhiqi Tian, Rui Chen, Guiqian Fang, Kangqiang Qiu, Weijun Wu, Xintian Shao, Daili Liu, Huilin Que, Xueqian Wang, Ji Gao, Jianyu Zhang, Bidyut Kumar Kundu
+7 more Qixin chen, Jun-Lin Guan, Yueguang Rong, Ben Zhong Tang, Kai Li, Yujie Sun, Jiajie Diao
DOI: 10.1016/j.celrep.2026.117112
Cited by: 7
References: 39

Abstract

The acidic environment within the lysosome lumen is essential for its digestive function. However, the source of protons responsible for acidification has remained elusive. Here, using a molecular probe to monitor lysosomal digestion, we discovered enhanced lysosome content degradation at mitochondria-lysosome contact (MLC) sites, which was caused by lysosomal acidification. Using a mitochondrial probe, we observed a proton flux from mitochondria to lysosomes at these MLC sites. Furthermore, we found that physically bringing mitochondria and lysosomes into close proximity can increase lysosome acidification to enhance content digestion under disease conditions. These findings unveil a crucial physiological role of MLCs in cellular functions.

Fields of Study & Subjects

Mitochondrial Function and Pathology ATP Synthase and ATPases Research Autophagy in Disease and Therapy

Publication details

Journal / source
Cell Reports
Publisher
Elsevier BV
Volume
45
Issue
3
Pages
117112–117112
Publication date
1 March 2026
Language
EN