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Dissection of Mitochondrial Function via Chemical Perturbation and Single-Cell Profiling.
Hao Luo1,2,3, Xiaona Yin1,2,3, Hongxin He1,2,3
1The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
Cell Proliferation
|April 27, 2026
Summary
Mitochondrial homeostasis relies on coordinated modules, not single genes. This study used single-cell RNA sequencing to map cellular responses to mitochondrial dysfunction, revealing shared and specific transcriptional programs and cell cycle impacts.
Area of Science:
- Cellular Biology
- Mitochondrial Biology
- Systems Biology
Background:
- Mitochondrial homeostasis is crucial for cellular function, involving complex modules like metabolism, dynamics, and signaling.
- Understanding how disruptions in these modules affect cellular states is essential but incomplete.
Purpose of the Study:
- To systematically profile transcriptional responses to perturbations of core mitochondrial functional modules.
- To identify shared and module-specific transcriptional programs and their impact on cellular states.
Main Methods:
- Utilized targeted chemical perturbations combined with single-cell RNA sequencing (scRNA-seq).
- Performed comparative analyses of transcriptional responses across different mitochondrial module inhibitions.
- Investigated cell-cycle dynamics and cross-species conservation of responses.
Main Results:
- Identified both shared and module-specific transcriptional programs, with recurrent co-expression patterns.
- Implicated mitochondrial reactive oxygen species (mtROS) in regulating mitochondrial respiratory chain (MRC) gene expression via the mitochondrial integrated stress response (mtISR).
- Demonstrated distinct cellular and transcriptional consequences for different MRC complex perturbations, including cell-cycle arrest (G1 or G2/M phase).
Conclusions:
- Established a systematic single-cell framework for dissecting mitochondrial functional modules.
- Highlighted shared and function-specific principles governing cellular transcriptional states under mitochondrial stress.
- Revealed conserved and divergent responses between human and mouse cells.
