Mitophagy disorder mediates cardiac deterioration induced by severe hypoglycemia in diabetic mice

Huang, Cuihua; Huang, Lishan; Huang, Qiulan; Lin, Lu; Wang, Lijing; Wu, Yubin; Wu, Ke‐Jun; Gao, Ruonan; Liu, Xiaoying; Liu, Xiaohong; Qi, Liqin; Liu, Libin

doi:10.1016/j.mce.2023.111994

Cited by 2 publications

(1 citation statement)

References 44 publications

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“…In the myocardium, autophagy and mitophagy are particularly important as cardiomyocytes, the main functional cells that undergo continuous contractions, require efficient cellular clearance to deal with various cellular and energetic stresses [ 8 , 9 ]. A growing number of studies have found that these cellular clearance pathways are impaired in cardiac pathologies, including diabetes [ 10 , 11 , 12 , 13 ]; however, their precise roles in cardiovascular diseases remain elusive. For example, while excessive cardiac autophagy might be detrimental in causing cell death and exaggerating cardiac insults, exercise training also promotes mitophagic activity and provides protection against heart failure [ 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555

Guan,

Zhang,

Lacy

et al. 2024

IJMS

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Millions of diabetic patients suffer from cardiovascular complications. One of the earliest signs of diabetic complications in the heart is diastolic dysfunction. Regular exercise is a highly effective preventive/therapeutic intervention against diastolic dysfunction in diabetes, but the underlying mechanism(s) remain poorly understood. Studies have shown that the accumulation of damaged or dysfunctional mitochondria in the myocardium is at the center of this pathology. Here, we employed a mouse model of diabetes to test the hypothesis that endurance exercise training mitigates diastolic dysfunction by promoting cardiac mitophagy (the clearance of mitochondria via autophagy) via S555 phosphorylation of Ulk1. High-fat diet (HFD) feeding and streptozotocin (STZ) injection in mice led to reduced endurance capacity, impaired diastolic function, increased myocardial oxidative stress, and compromised mitochondrial structure and function, which were all ameliorated by 6 weeks of voluntary wheel running. Using CRISPR/Cas9-mediated gene editing, we generated non-phosphorylatable Ulk1 (S555A) mutant mice and showed the requirement of p-Ulk1at S555 for exercise-induced mitophagy in the myocardium. However, diabetic Ulk1 (S555A) mice retained the benefits of exercise intervention. We conclude that endurance exercise training mitigates diabetes-induced diastolic dysfunction independent of Ulk1 phosphorylation at S555.

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Section: Introductionmentioning

confidence: 99%

Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555

Guan,

Zhang,

Lacy

et al. 2024

IJMS

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Urolithin A induces cardioprotection and enhanced mitochondrial quality during natural aging and heart failure

Liu,

Faitg,

Tissot

et al. 2023

Preprint

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Cardiovascular diseases remain the primary cause of global mortality, necessitating effective strategies to alleviate their burden. Mitochondrial dysfunction is a driving force behind aging and chronic conditions, including heart disease. Here, we investigate the potential of Urolithin A (UA), a gut microbiome-derived postbiotic that enhances mitophagy, to ameliorate both age-related decline in cardiac function and cardiac failure. We highlight the significance of targeting mitochondria, by comparing gene expression changes in aging human hearts and cardiomyopathies. UA oral administration successfully counteracts mitochondrial and cardiac dysfunctions in preclinical models of aging and heart failure. UA improves both systolic and diastolic heart functions, distinguishing it from other mitochondrial interventions. In cardiomyocytes, UA recovers mitochondrial ultrastructural defects and decline in mitochondrial biomarkers occurring with aging and disease. These findings extend UA?s benefits to heart health, making UA a promising nutritional intervention to evaluate in the clinic to promote healthy cardiovascular function as we age.

show abstract

Mitophagy disorder mediates cardiac deterioration induced by severe hypoglycemia in diabetic mice

Cited by 2 publications

References 44 publications

Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555

Endurance Exercise Training Mitigates Diastolic Dysfunction in Diabetic Mice Independent of Phosphorylation of Ulk1 at S555

Urolithin A induces cardioprotection and enhanced mitochondrial quality during natural aging and heart failure

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