Role and Mechanisms of Mitophagy in Liver Diseases

Ma, Xiaowen; McKeen, Tara; Zhang, Jianhua; Ding, Wen–Xing

doi:10.3390/cells9040837

Cited by 144 publications

(101 citation statements)

References 223 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lifestyle likewise impacts mitochondrial quality control systems, as evidenced by studies showing, for example, how physically active men have a higher expression of mitochondrial fission and mitophagy markers than sedentary men, while overfeeding, a risk factor of such pathologies as CVD and liver disease, is related to the accumulation of damaged mitochondria and oxidative stress [ 400 ]. This is likely related to the decreased activity of AMPK, a protein that activates mitochondrial biogenesis and mitophagy in response to low nutrient availability through the activation of ULK1 [ 401 ] and PGC-1α, respectively [ 253 ]. As indicated before, AMPK also induces SIRT1 activity, an nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase, that in turn activates PGC-1α.…”

Section: Mitophagy and Lifestyle Impact On Agingmentioning

confidence: 99%

Mitophagy in Human Diseases

Doblado

Lueck

Rey

et al. 2021

IJMS

View full text Add to dashboard Cite

Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria. Activated by inner membrane depolarization, it plays an important role during development and is fundamental in highly differentiated post-mitotic cells that are highly dependent on aerobic metabolism, such as neurons, muscle cells, and hepatocytes. Both defective and excessive mitophagy have been proposed to contribute to age-related neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, metabolic diseases, vascular complications of diabetes, myocardial injury, muscle dystrophy, and liver disease, among others. Pharmacological or dietary interventions that restore mitophagy homeostasis and facilitate the elimination of irreversibly damaged mitochondria, thus, could serve as potential therapies in several chronic diseases. However, despite extraordinary advances in this field, mainly derived from in vitro and preclinical animal models, human applications based on the regulation of mitochondrial quality in patients have not yet been approved. In this review, we summarize the key selective mitochondrial autophagy pathways and their role in prevalent chronic human diseases and highlight the potential use of specific interventions.

show abstract

Section: Mitophagy and Lifestyle Impact On Agingmentioning

confidence: 99%

Mitophagy in Human Diseases

Doblado

Lueck

Rey

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Selective degradation of damaged mitochondria by autophagy, also termed mitophagy, helps to maintain the integrity of cell function. Recent evidence has shown that the induction of mitophagy prevents high-fat-diet-induced liver injury [ 57 , 58 ]. In addition, PA decreased mitophagy, leading to mitochondrial dysfunction characterized by extensive mito-ROS production and MMP loss [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes

Song

Zhou

et al. 2021

Nutr Metab (Lond)

View full text Add to dashboard Cite

Background Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective effect of ferulic acid against palmitate-induced lipotoxicity and clarified its potential mechanisms in AML-12 hepatocytes. Methods AML-12 mouse hepatocytes were exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate treatment. Cell viability was detected by measuring lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase-3. Intracellular reactive oxygen species content and mitochondrial membrane potential were analysed by fluorescent probes. The potential mechanisms were explored by molecular biological methods, including Western blotting and quantitative real-time PCR, and were further verified by siRNA interference. Results Our data showed that ferulic acid significantly inhibited palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxygen species accumulation, and decreased inflammatory factor activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, whereas autophagy suppression blocked the protective effect of ferulic acid against lipotoxicity. Ferulic acid-activated autophagy, which was triggered by SIRT1 upregulation, was mechanistically involved in its anti-lipotoxicity effects. SIRT1 silencing blocked most beneficial changes induced by ferulic acid. Conclusions We demonstrated that the phytochemical ferulic acid, which is found in plant-based food, protected against hepatic lipotoxicity, through the SIRT1/autophagy pathway. Increased intake of ferulic acid-enriched food is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature.

show abstract

“…Selective degradation of damaged mitochondrial by autophagy was also termed as mitophagy, which helped to maintain the integrity of the cell function. Recent evidence has provided that the induction of mitophagy prevented high-fat diet-induced liver injury [54,55]. Besides, PA-decreased mitophagy, leading to mitochondrial dysfunction as characterized by extensive mito-ROS production and loss of MMP [56].…”

Section: Discussionmentioning

confidence: 99%

Ferulic Acid Alleviates Lipotoxicity-induced Hepatocellular Death Through SIRT1 Activating-regulated Autophagy Pathway, and Independently of AMPK and Akt in AML-12 Hepatocytes

Song

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Lipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in vegetative food, is conferred as a radical scavenger with multiple bioactivities. However, the benefits of Ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective role of ferulic acid on palmitate-induced lipotoxicity and clarify its potential mechanisms in AML-12 hepatocytes. Methods: AML-12 mouse hepatocyte was employed and exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate induction. Cell viability was detected by the measurements of lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase3. Intracellular reactive oxygen species and mitochondrial membrane potential were analyzed by fluorescent probe. The potential mechanisms were explored by molecular biological methods, including Western-blot and quantitative real-time PCR, and further verified by siRNA interference. Results: Our data showed that ferulic acid significantly reversed palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxidative species accumulation, and improved inflammatory factors activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, while, autophagy suppression blocked ferulic acid-protected lipotoxicity. Ferulic acid-activated autophagy, which was triggered by Sirt1 upregulation, was mechanistically involved in its anti-lipotoxicity benefits. Sirt1 silencing blocked ferulic acid-induced profitable alterations. Conclusions: We demonstrated that ferulic acid was a protective phytochemical against hepatic lipotoxicity in plant-based food, through Sirt1/autophagy pathway. Increasing ferulic acid-enriched food intake is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature.

show abstract

Role and Mechanisms of Mitophagy in Liver Diseases

Cited by 144 publications

References 223 publications

Mitophagy in Human Diseases

Mitophagy in Human Diseases

Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes

Ferulic Acid Alleviates Lipotoxicity-induced Hepatocellular Death Through SIRT1 Activating-regulated Autophagy Pathway, and Independently of AMPK and Akt in AML-12 Hepatocytes

Contact Info

Product

Resources

About