Yeast Mitochondrial Escape 1-Like as a Mitochondrial Gatekeeper in Aging-Related Cardiovascular Disease
- 1Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China
Abstract
Mitochondrial dysfunction is a hallmark of aging and is closely linked to the progression of cardiovascular disease. Yeast mitochondrial escape 1-like (YME1L) is an adenosine triphosphate (ATP)-dependent i-AAA (intermembrane space AAA, AAA=ATPase associated with diverse cellular activities) protease embedded in the mitochondrial inner membrane that maintains mitochondrial homeostasis by regulating proteostasis, cristae architecture, and metabolic adaptation. Notably, YME1L influences mitochondrial fusion–fission dynamics, respiratory chain supercomplex organization, and oxidative phosphorylation efficiency through the regulated processing of optic atrophy protein 1 (OPA1). Accumulating evidence suggests that age-associated impairment of YME1L function contributes to mitochondrial fragmentation, energetic insufficiency, and reduced stress tolerance, particularly in long-lived, high-energy demand tissues. In the cardiovascular system, experimental models indicate that YME1L deficiency disrupts cristae organization, promotes maladaptive metabolic remodeling, and promotes heart failure-like phenotypes. Conversely, preservation of YME1L activity supports mitochondrial integrity and enhances cardiac resilience under hemodynamic stress. In addition to cardiomyocytes, YME1L also supports endothelial mitochondrial homeostasis, thereby linking mitochondrial proteostasis to vascular aging and diastolic dysfunction. Although YME1L has been extensively studied in cancer biology, its relevance to aging-related cardiovascular vulnerability is increasingly recognized, especially in cardio-oncology, where therapy-induced mitochondrial stress may be exacerbated by age-dependent decline in mitochondrial quality control. This review integrates current evidence supporting YME1L as a context-dependent regulator of mitochondrial stress adaptation, with particular emphasis on the roles of YME1L in cardiovascular aging, heart failure with preserved ejection fraction (HFpEF), and stress tolerance. Rather than positioning YME1L as a universal therapeutic target, we discuss how modulating YME1L-associated pathways may help preserve mitochondrial resilience and mitigate age-related cardiovascular dysfunction.
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BibTeX
@article{wan2026yeast,
title = {{Yeast Mitochondrial Escape 1-Like as a Mitochondrial Gatekeeper in Aging-Related Cardiovascular Disease}},
author = {Zhihao Wan and Xiaorong Li and Xiaoli Zhou and Yongzheng Guo},
journal = {Reviews in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.31083/rcm49477},
url = {https://doi.org/10.31083/rcm49477},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Yeast Mitochondrial Escape 1-Like as a Mitochondrial Gatekeeper in Aging-Related Cardiovascular Disease
AU - Zhihao Wan
AU - Xiaorong Li
AU - Xiaoli Zhou
AU - Yongzheng Guo
PY - 2026
DA - 2026/10/21
JO - Reviews in Cardiovascular Medicine
DO - 10.31083/rcm49477
UR - https://doi.org/10.31083/rcm49477
AB - Mitochondrial dysfunction is a hallmark of aging and is closely linked to the progression of cardiovascular disease. Yeast mitochondrial escape 1-like (YME1L) is an adenosine triphosphate (ATP)-dependent i-AAA (intermembrane space AAA, AAA=ATPase associated with diverse cellular activities) protease embedded in the mitochondrial inner membrane that maintains mitochondrial homeostasis by regulating proteostasis, cristae architecture, and metabolic adaptation. Notably, YME1L influences mitochondrial fusion–fission dynamics, respiratory chain supercomplex organization, and oxidative phosphorylation efficiency through the regulated processing of optic atrophy protein 1 (OPA1). Accumulating evidence suggests that age-associated impairment of YME1L function contributes to mitochondrial fragmentation, energetic insufficiency, and reduced stress tolerance, particularly in long-lived, high-energy demand tissues. In the cardiovascular system, experimental models indicate that YME1L deficiency disrupts cristae organization, promotes maladaptive metabolic remodeling, and promotes heart failure-like phenotypes. Conversely, preservation of YME1L activity supports mitochondrial integrity and enhances cardiac resilience under hemodynamic stress. In addition to cardiomyocytes, YME1L also supports endothelial mitochondrial homeostasis, thereby linking mitochondrial proteostasis to vascular aging and diastolic dysfunction. Although YME1L has been extensively studied in cancer biology, its relevance to aging-related cardiovascular vulnerability is increasingly recognized, especially in cardio-oncology, where therapy-induced mitochondrial stress may be exacerbated by age-dependent decline in mitochondrial quality control. This review integrates current evidence supporting YME1L as a context-dependent regulator of mitochondrial stress adaptation, with particular emphasis on the roles of YME1L in cardiovascular aging, heart failure with preserved ejection fraction (HFpEF), and stress tolerance. Rather than positioning YME1L as a universal therapeutic target, we discuss how modulating YME1L-associated pathways may help preserve mitochondrial resilience and mitigate age-related cardiovascular dysfunction.
SN - 1530-6550
SN - 2153-8174
ER -