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RESEARCH PAPER / 2025-09-22

Cross-Organ Mitochondrial Communication in Stress and Disease.

Koning Shen, Jenni Durieux, Andrew Dillin

1Department of Molecular and Cell Biology, University of California, Berkeley, California, USA; email: [email protected] of Molecular and Cell Biology, University of California, Berkeley, California, USA; email: [email protected]. · pubmed

Abstract

Growing evidence points to mitochondria as not just the "powerhouse of the cell" but as a major cellular hub for signaling. Mitochondria use signaling pathways to communicate with other organelles within the cell or organs within an organism to regulate stress response, metabolic, immune, and longevity pathways. These communication pathways are carried out by mitokine signaling molecules encompassing metabolites, lipids, proteins, and even whole mitochondrial organelles themselves. In this review, we focus on the communication pathways mitochondria use to communicate between different organs in invertebrates, mammalian models, and humans. We cover the molecular events that trigger communication, the signaling mechanisms themselves, and the impact this communication has on organismal health in the context of stress and disease. Further understanding of cross-organ mitochondrial communication pathways will inform the design of therapeutics that take advantage of their protective effects to treat diseases associated with mitochondrial dysfunction.

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Research summary

Mitochondria communicate across organs to regulate stress response and longevity pathways. This paper is relevant as it explores mechanisms that could address the root causes of aging through mitochondrial communication, potentially informing therapeutic strategies for age-related diseases.

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