Extracellular Mitochondrial Components as Emerging Biomarkers and Therapeutic Targets in Human Diseases.
7 affiliations
- 1Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
- 2Institute of Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.
- 3Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
- 4Sundial Initiative, Palo Alto, CA, 94304, USA.
- 5Division of Urology, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
- 6Center of General Education, Cheng Shiu University, Kaohsiung 833, Taiwan.
- 7National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan.
Abstract
Mitochondria serve as the bioenergetic hub of eukaryotic cells while simultaneously acting as a major source of cellular stress and toxicity. Classical mitochondrial quality control (MQC) has long been viewed as a lysosome-dependent process centered on mitophagy. However, aging is accompanied by progressive lysosomal dysfunction, limiting the efficiency of canonical mitochondrial clearance and contributing to mitochondrial accumulation and cellular deterioration. Emerging evidence suggests that under conditions of lysosomal overload and metabolic stress, cells engage alternative quality-control pathways by selectively exporting mitochondrial components into the extracellular environment through mitochondrial-derived vesicles (MDVs) and exophers. In this review, we integrate current findings to propose a unified framework of age-associated mitochondrial disposition and discuss how cells dynamically balance intracellular degradation with extracellular mitochondrial secretion. We further examine the molecular machinery underlying MDV and exopher biogenesis and evaluate their roles in reshaping intercellular metabolic communication. Particular emphasis is placed on their translational relevance in cancer and neurodegenerative disorders, where extracellular mitochondrial trafficking may contribute to disease progression, therapeutic resistance, and tissue remodeling. We also discuss the technical and analytical bottlenecks that currently constrain this field. Finally, we discuss the emerging potential of mitochondrial secretion pathways as diagnostic biomarkers and therapeutic targets for age-associated diseases.
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BibTeX
@article{tsui2026extracellular,
title = {{Extracellular Mitochondrial Components as Emerging Biomarkers and Therapeutic Targets in Human Diseases.}},
author = {Kuan-Hao Tsui and Emmanuel Naveen Raj and Andy P Tsai and Boyang Wang and Chen-Yueh Wen and Chia-Jung Li},
journal = {International journal of biological sciences},
year = {2026},
month = sep,
doi = {10.7150/ijbs.140360},
url = {https://europepmc.org/article/MED/42910279},
note = {CC BY},
}
RIS
TY - JOUR
TI - Extracellular Mitochondrial Components as Emerging Biomarkers and Therapeutic Targets in Human Diseases.
AU - Kuan-Hao Tsui
AU - Emmanuel Naveen Raj
AU - Andy P Tsai
AU - Boyang Wang
AU - Chen-Yueh Wen
AU - Chia-Jung Li
PY - 2026
DA - 2026/09/24
JO - International journal of biological sciences
DO - 10.7150/ijbs.140360
UR - https://europepmc.org/article/MED/42910279
AB - Mitochondria serve as the bioenergetic hub of eukaryotic cells while simultaneously acting as a major source of cellular stress and toxicity. Classical mitochondrial quality control (MQC) has long been viewed as a lysosome-dependent process centered on mitophagy. However, aging is accompanied by progressive lysosomal dysfunction, limiting the efficiency of canonical mitochondrial clearance and contributing to mitochondrial accumulation and cellular deterioration. Emerging evidence suggests that under conditions of lysosomal overload and metabolic stress, cells engage alternative quality-control pathways by selectively exporting mitochondrial components into the extracellular environment through mitochondrial-derived vesicles (MDVs) and exophers. In this review, we integrate current findings to propose a unified framework of age-associated mitochondrial disposition and discuss how cells dynamically balance intracellular degradation with extracellular mitochondrial secretion. We further examine the molecular machinery underlying MDV and exopher biogenesis and evaluate their roles in reshaping intercellular metabolic communication. Particular emphasis is placed on their translational relevance in cancer and neurodegenerative disorders, where extracellular mitochondrial trafficking may contribute to disease progression, therapeutic resistance, and tissue remodeling. We also discuss the technical and analytical bottlenecks that currently constrain this field. Finally, we discuss the emerging potential of mitochondrial secretion pathways as diagnostic biomarkers and therapeutic targets for age-associated diseases.
SN - 1449-2288
ER -