Pentacyclic triterpene oleanolic acid protects against cardiac aging through regulation of mitophagy and mitochondrial integrity

Gong, Yan; Luo, Yuanfei; Liu, Suqin; Ma, Jie; Liu, Fangpeng; Fang, Yan; Cao, Feng; Wang, Lin; Pei, Zhaohui; Ren, Jun

doi:10.1016/j.bbadis.2022.166402

Cited by 24 publications

(12 citation statements)

References 41 publications

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“…Echocardiographic evaluation shows that aging mainly affects the diastolic function in male C57BL/6 mice [ 63 ]. Aging also leads to decreased contractility in isolated cardiomyocytes [ 64 ]. These results indicate that aging may affect both systolic and diastolic function.…”

Section: Discussionmentioning

confidence: 99%

Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria

Chen¹,

Thompson²,

Hu³

et al. 2022

Life

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Background: Induction of acute ER (endoplasmic reticulum) stress using thapsigargin contributes to complex I damage in mouse hearts. Thapsigargin impairs complex I by increasing mitochondrial calcium through inhibition of Ca2+-ATPase in the ER. Tunicamycin (TUNI) is used to induce ER stress by inhibiting protein folding. We asked if TUNI-induced ER stress led to complex I damage. Methods: TUNI (0.4 mg/kg) was used to induce ER stress in C57BL/6 mice. Cardiac mitochondria were isolated after 24 or 72 h following TUNI treatment for mitochondrial functional analysis. Results: ER stress was only increased in mice following 72 h of TUNI treatment. TUNI treatment decreased oxidative phosphorylation with complex I substrates compared to vehicle with a decrease in complex I activity. The contents of complex I subunits including NBUPL and NDUFS7 were decreased in TUNI-treated mice. TUNI treatment activated both cytosolic and mitochondrial calpain 1. Our results indicate that TUNI-induced ER stress damages complex I through degradation of its subunits including NDUFS7. Conclusion: Induction of the ER stress using TUNI contributes to complex I damage by activating calpain 1.

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Section: Discussionmentioning

confidence: 99%

Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria

Chen¹,

Thompson²,

Hu³

et al. 2022

Life

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“…Although substantial progresses were achieved for the role of mitophagy in CVDs (Ajoolababy et al, 2020;Ajoolababy et al, 2022), the precise regulatory mechanisms, especially in connection with kinases and phosphorylation, remains to be explored. Recent finding from our group indicated a beneficial role for pentacyclic triterpene oleanolic acid in facilitating FUNDC1-mediated mitophagy (Gong et al, 2022), although drug development for small molecule regulator of FUNDC1 remains dismal. Moreover, moderate controllability of mitophagy is rather difficult to handle, thus making application of mitophagy inducers rather challenging.…”

Section: Discussionmentioning

confidence: 98%

FUN14 Domain Containing 1 (FUNDC1): A Promising Mitophagy Receptor Regulating Mitochondrial Homeostasis in Cardiovascular Diseases

2022

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Mitochondria, the intracellular organelles for cellular aerobic respiration and energy production, play an important role in the regulation of cell metabolism and cell fate. Mitophagy, a selective form of autophagy, maintains dynamic homeostasis of cells through targeting long-lived or defective mitochondria for timely clearance and recycling. Dysfunction in mitophagy is involved in the molecular mechanism responsible for the onset and development of human diseases. FUN14 domain containing 1 (FUNDC1) is a mitochondrial receptor located in the outer mitochondria membrane (OMM) to govern mitophagy process. Emerging evidence has demonstrated that levels and phosphorylation states of FUNDC1 are closely related to the occurrence, progression and prognosis of cardiovascular diseases, indicating a novel role for this mitophagy receptor in the regulation of mitochondrial homeostasis in cardiovascular system. Here we review mitophagy mediated by FUNDC1 in mitochondria and its role in various forms of cardiovascular diseases.

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“…In recent years, Parkin has emerged as a critical player in the defense against mitochondrial dysfunction and muscle atrophy. Evidence shows that Parkin deficiency disrupts mitophagy and contributes to chronic obstructive pulmonary disease, and these effects are accompanied by increased mitochondrial ROS levels and muscle atrophy [98]. Furthermore, Parkin-deficient muscle shows impaired mitochondrial respiration, mitochondrial fragmentation, and sensitization of the mitochondrial permeability transition pore [99].…”

Section: Mitophagy Aberrations In Aging Skeletal Musclementioning

confidence: 99%

Exercise Improves the Coordination of the Mitochondrial Unfolded Protein Response and Mitophagy in Aging Skeletal Muscle

Wang

Zhang

et al. 2023

Life

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The mitochondrial unfolded protein response (UPRmt) and mitophagy are two mitochondrial quality control (MQC) systems that work at the molecular and organelle levels, respectively, to maintain mitochondrial homeostasis. Under stress conditions, these two processes are simultaneously activated and compensate for each other when one process is insufficient, indicating mechanistic coordination between the UPRmt and mitophagy that is likely controlled by common upstream signals. This review focuses on the molecular signals regulating this coordination and presents evidence showing that this coordination mechanism is impaired during aging and promoted by exercise. Furthermore, the bidirectional regulation of reactive oxygen species (ROS) and AMPK in modulating this mechanism is discussed. The hierarchical surveillance network of MQC can be targeted by exercise-derived ROS to attenuate aging, which offers a molecular basis for potential therapeutic interventions for sarcopenia.

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Pentacyclic triterpene oleanolic acid protects against cardiac aging through regulation of mitophagy and mitochondrial integrity

Cited by 24 publications

References 41 publications

Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria

Tunicamycin-Induced Endoplasmic Reticulum Stress Damages Complex I in Cardiac Mitochondria

FUN14 Domain Containing 1 (FUNDC1): A Promising Mitophagy Receptor Regulating Mitochondrial Homeostasis in Cardiovascular Diseases

Exercise Improves the Coordination of the Mitochondrial Unfolded Protein Response and Mitophagy in Aging Skeletal Muscle

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