Peer-reviewedCC BYAmerican journal of physiology. Heart and circulatory physiology
Impaired mitochondrial proteostasis underlies cardiomyocyte bioenergetic dysfunction in a murine 3-hit model of heart failure with preserved ejection fraction
- 1Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216
Abstract
Heart failure with preserved ejection fraction (HFpEF) lacks effective therapies in part due to an incomplete understanding of cardiomyocyte-specific mitochondrial mechanisms involved in cardiac dysfunction. Using an aged, multihit mouse model that recapitulates key features of human HFpEF in both sexes, we demonstrate that impaired cardiac reserve is associated with reduced mitochondrial respiratory capacity and coordinated suppression of mitochondrial protein quality-control pathways. These findings identify mitochondrial proteostasis failure as a central mechanism limiting energetic reserve in HFpEF cardiomyocytes.
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BibTeX
@article{li2026impaired,
title = {{Impaired mitochondrial proteostasis underlies cardiomyocyte bioenergetic dysfunction in a murine 3-hit model of heart failure with preserved ejection fraction}},
author = {Xuan Li and Yiling Fu and Jussara M. do Carmo and Alexandre A. da Silva and Alan J. Mouton and Ana C.M. Omoto and Lucas Wang and John E. Hall and Zhen Wang},
journal = {American journal of physiology. Heart and circulatory physiology},
year = {2026},
month = sep,
doi = {10.1152/ajpheart.00304.2026},
url = {https://doi.org/10.1152/ajpheart.00304.2026},
note = {CC BY},
}
RIS
TY - JOUR
TI - Impaired mitochondrial proteostasis underlies cardiomyocyte bioenergetic dysfunction in a murine 3-hit model of heart failure with preserved ejection fraction
AU - Xuan Li
AU - Yiling Fu
AU - Jussara M. do Carmo
AU - Alexandre A. da Silva
AU - Alan J. Mouton
AU - Ana C.M. Omoto
AU - Lucas Wang
AU - John E. Hall
AU - Zhen Wang
PY - 2026
DA - 2026/09/19
JO - American journal of physiology. Heart and circulatory physiology
DO - 10.1152/ajpheart.00304.2026
UR - https://doi.org/10.1152/ajpheart.00304.2026
AB - Heart failure with preserved ejection fraction (HFpEF) lacks effective therapies in part due to an incomplete understanding of cardiomyocyte-specific mitochondrial mechanisms involved in cardiac dysfunction. Using an aged, multihit mouse model that recapitulates key features of human HFpEF in both sexes, we demonstrate that impaired cardiac reserve is associated with reduced mitochondrial respiratory capacity and coordinated suppression of mitochondrial protein quality-control pathways. These findings identify mitochondrial proteostasis failure as a central mechanism limiting energetic reserve in HFpEF cardiomyocytes.
SN - 0363-6135
SN - 1522-1539
ER -