Mitochondrial quality control mechanisms as molecular targets in diabetic heart

Chang, Xing; Li, Yukun; Cai, Chen; Wu, Feng; He, Jing; Zhang, Yaoyuan; Zhong, Jian‐Jiang; Tan, Ying; Liu, Ruxiu; Zhu, Hang; Zhou, Hao

doi:10.1016/j.metabol.2022.155313

Cited by 75 publications

(36 citation statements)

References 129 publications

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“…Under stress conditions, mitochondrial damage is counteracted by activation of an endogenous repair mechanism, which coordinates mitochondrial division/fusion and biogenesis [16][17][18][19][20]. Another crucial process controlled by the MQC is mitochondrial autophagy (mitophagy), a PINK1/Parkin pathway-dependent process that serves to recycle the components of defective mitochondria to stabilize the mitochondrial network [21][22][23][24]. Studies from our laboratory [25] and others [26,27] have confirmed the protective effects of mitophagy in the setting of ALD.…”

Section: Ivyspringmentioning

confidence: 71%

Interaction between dual specificity phosphatase-1 and cullin-1 attenuates alcohol-related liver disease by restoring p62-mediated mitophagy

Li¹,

Dai²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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Besides abstinence, no effective treatment exists for alcohol-related liver disease (ALD), a dreaded consequence of alcohol abuse. In this study, we assessed the roles on ALD of dual specificity phosphatase-1 (DUSP1), an hepatoprotective enzyme, and Cullin-1 (CUL1), a member of the E3 ubiquitin ligase complex that exerts also transcriptional suppression of mitochondrial genes. Alcohol treatment downregulated hepatic DUSP1 expression in wild-type mice. Notably, DUSP1 transgenic ( Dusp1 Tg ) mice showed resistance to alcohol-mediated hepatic dysfunction, as evidenced by decreased AST/ALT activity, improved alcohol metabolism, and suppressed liver fibrosis, inflammation, and oxidative stress. Functional experiments demonstrated that DUSP1 overexpression prevents alcohol-mediated mitochondrial damage in hepatocytes through restoring mitophagy. Accordingly, pharmacological blockade of mitophagy abolished the hepatoprotective actions of DUSP1. Molecular assays showed that DUSP1 binds cytosolic CUL1 and prevents its translocation to the nucleus. Importantly, CUL1 silencing restored the transcription of p62 and Parkin, resulting in mitophagy activation, and sustained mitochondrial integrity and hepatocyte function upon alcohol stress. These results indicate that alcohol-mediated DUSP1 downregulation interrupts DUSP1/CUL1 interaction, leading to CUL1 nuclear translocation and mitophagy inhibition via transcriptional repression of p62 and Parkin. Thus, targeting the DUSP1/CUL1/p62 axis will be a key approach to restore hepatic mitophagy as well as alleviate symptoms of ALD.

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Section: Ivyspringmentioning

confidence: 71%

Interaction between dual specificity phosphatase-1 and cullin-1 attenuates alcohol-related liver disease by restoring p62-mediated mitophagy

Li¹,

Dai²,

Liu³

et al. 2023

Int. J. Biol. Sci.

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“…Mitochondrial dysfunction is well known to induce or exacerbate cardiac I/R injury [39,[49][50][51][52]. I/R injury causes excessive mitochondrial fission, and the resulting fragmented mitochondria exhibit reduced ATP production [39,53,54].…”

Section: Discussionmentioning

confidence: 99%

Transmembrane BAX inhibitor motif containing 6 suppresses presenilin-2 to preserve mitochondrial integrity after myocardial ischemia-reperfusion injury

Ma¹,

Liao²,

Zhou³

et al. 2023

Int. J. Biol. Sci.

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Myocardial ischemia-reperfusion (I/R) damage is characterized by mitochondrial damage in cardiomyocytes. Transmembrane BAX inhibitor motif containing 6 (TMBIM6) and presenilin-2 (PS2) participate in multiple mitochondrial pathways; thus, we investigated the impact of these proteins on mitochondrial homeostasis during an acute reperfusion injury. Myocardial post-ischemic reperfusion stress impaired myocardial function, induced structural abnormalities and promoted cardiomyocyte death by disrupting the mitochondrial integrity in wild-type mice, but not in TMBIM6 transgenic mice. We found that TMBIM6 bound directly to PS2 and promoted its post-transcriptional degradation. Knocking out PS2 in mice reduced I/R injury-induced cardiac dysfunction, inflammatory responses, myocardial swelling and cardiomyocyte death by improving the mitochondrial integrity. These findings demonstrate that sufficient TMBIM6 expression can prevent PS2 accumulation during cardiac I/R injury, thus suppressing reperfusion-induced mitochondrial damage. Therefore, TMBIM6 and PS2 are promising therapeutic targets for the treatment of cardiac reperfusion damage.

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“…Many processes control mitochondrial quality, such as mitochondrial retrograde response, mitochondrial dynamics, and mitophagy. [8,9] An increasing body of evidence from recent studies has shown that impaired mitochondrial quality control can exacerbate sepsis-induced ALI while restoring mitochondrial quality control can improve it. [10][11][12] Overall, modulating mitochondrial quality control is a potential therapeutic strategy in sepsis-induced ALI.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with Kahweol Attenuates Sepsis‐Induced Acute Lung Injury via Improving Mitochondrial Homeostasis in a CaMKKII/AMPK‐Dependent Pathway

Wang

et al. 2023

Molecular Nutrition Food Res

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ScopeIt is well‐established that dysregulated mitochondrial homeostasis in macrophages leads to inflammation, oxidative stress, and tissue damage, which are essential in the pathogenesis of sepsis‐induced acute lung injury (ALI). Kahweol, a natural diterpene extracted from coffee beans, reportedly possesses anti‐inflammatory and mitochondrial protective properties. Herein, the study investigates whether Kahweol can alleviate sepsis‐induced ALI and explore the underlying mechanisms.Methods and resultsC57BL/6J mice are intraperitoneally injected with lipopolysaccharide (LPS) for 12 h to induce ALI. Pretreatment with kahweol by gavage for 5 days significantly alleviates lung pathological injury, inflammation, and oxidative stress, accompanied by shifting the dynamic process of mitochondria from fission to fusion, enhancing mitophagy, and activating AMPK. To investigate the underlying molecular mechanisms, differentiated THP‐1 cells are cultured in a medium containing Kahweol for 12 h prior to LPS exposure, yielding consistent findings with the in vivo results. Moreover, AMPK inhibitors abrogate the above effects, indicating Kahweol acts in an AMPK‐dependent manner. Furthermore, the study explores how Kahweol activates AMPK and finds that this process is mediated by CamKK II.ConclusionPretreatment with Kahweol attenuates sepsis‐induced acute lung injury via improving mitochondrial homeostasis in a CaMKKII/AMPK‐dependent pathway and may be a potential candidate to prevent sepsis‐induced ALI.

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Mitochondrial quality control mechanisms as molecular targets in diabetic heart

Cited by 75 publications

References 129 publications

Interaction between dual specificity phosphatase-1 and cullin-1 attenuates alcohol-related liver disease by restoring p62-mediated mitophagy

Interaction between dual specificity phosphatase-1 and cullin-1 attenuates alcohol-related liver disease by restoring p62-mediated mitophagy

Transmembrane BAX inhibitor motif containing 6 suppresses presenilin-2 to preserve mitochondrial integrity after myocardial ischemia-reperfusion injury

Pretreatment with Kahweol Attenuates Sepsis‐Induced Acute Lung Injury via Improving Mitochondrial Homeostasis in a CaMKKII/AMPK‐Dependent Pathway

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