The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases

Zhang, Weilin

doi:10.1016/j.gendis.2020.08.011

Cited by 38 publications

(21 citation statements)

References 68 publications

(255 reference statements)

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“…FUN14 domain-containing 1 (FUNDC1) contains a conserved LC3-interacting region (LIR). Accumulating study confirms that FUNDC1 is a crucial hypoxia-mediated mitophagy regulator ( Chen et al, 2017 ; Li et al, 2018 ; Zhang, 2020 ). Similar to BNIP3/NIX, FUNDC1 directly interacts with LC3 through its LIR under hypoxic conditions ( Kuang et al, 2016 ).…”

Section: Mitophagy Signaling Pathwaysmentioning

confidence: 86%

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Guo

Huang

et al. 2021

Front. Cell Dev. Biol.

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Metabolic disorders include metabolic syndrome, obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular diseases. Due to unhealthy lifestyles such as high-calorie diet, sedentary and physical inactivity, the prevalence of metabolic disorders poses a huge challenge to global human health, which is the leading cause of global human death. Mitochondrion is the major site of adenosine triphosphate synthesis, fatty acid β−oxidation and ROS production. Accumulating evidence suggests that mitochondrial dysfunction-related oxidative stress and inflammation is involved in the development of metabolic disorders. Mitophagy, a catabolic process, selectively degrades damaged or superfluous mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial function. It is considered to be one of the major mechanisms responsible for mitochondrial quality control. Growing evidence shows that mitophagy can prevent and treat metabolic disorders through suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. In the past decade, in order to expand the range of pharmaceutical options, more and more phytochemicals have been proven to have therapeutic effects on metabolic disorders. Many of these phytochemicals have been proved to activate mitophagy to ameliorate metabolic disorders. Given the ongoing epidemic of metabolic disorders, it is of great significance to explore the contribution and underlying mechanisms of mitophagy in metabolic disorders, and to understand the effects and molecular mechanisms of phytochemicals on the treatment of metabolic disorders. Here, we investigate the mechanism of mitochondrial dysfunction in metabolic disorders and discuss the potential of targeting mitophagy with phytochemicals for the treatment of metabolic disorders, with a view to providing a direction for finding phytochemicals that target mitophagy to prevent or treat metabolic disorders.

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Section: Mitophagy Signaling Pathwaysmentioning

confidence: 86%

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Guo

Huang

et al. 2021

Front. Cell Dev. Biol.

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“…FUN14 domain-containing 1 (FUNDC1) is a newly identified mitochondrial outer membrane protein as well as LC3B-conjugated protein (mitophagy inducer) to modulate mitochondrial quality control. Mice depleted with FUNDC1 exhibited more severe obesity and insulin resistance due to mitophagy dysfunctions [ 29 , 30 ].…”

Section: Autophagy Related Genes and Type 2 Diabetes Mellitus Treatmentmentioning

confidence: 99%

Mitophagy and mitochondrial dynamics in type 2 diabetes mellitus treatment

Zhao

Tian

et al. 2022

Aging

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The prevalence of type 2 diabetes is associated with inflammatory bowels diseases, nonalcoholic steatohepatitis and even a spectrum of cancer such as colon cancer and liver cancer, resulting in a substantial healthcare burden on our society. Autophagy is a key regulator in metabolic homeostasis such as lipid metabolism, energy management and the balance of cellular mineral substances. Mitophagy is selective autophagy for clearing the damaged mitochondria and dysfunctional mitochondria. A myriad of evidence has demonstrated a major role of mitophagy in the regulation of type 2 diabetes and metabolic homeostasis. It is well established that defective mitophagy has been linked to the development of insulin resistance. Moreover, insulin resistance is further progressed to various diseases such as nephropathy, retinopathy and cardiovascular diseases. Concordantly, restoration of mitophagy will be a reliable and therapeutic target for type 2 diabetes. Recently, various phytochemicals have been proved to prevent dysfunctions of β-cells by mitophagy inductions during diabetes developments. In agreement with the above phenomenon, mitophagy inducers should be warranted as potential and novel therapeutic agents for treating diabetes. This review focuses on the role of mitophagy in type 2 diabetes relevant diseases and the pharmacological basis and therapeutic potential of autophagy regulators in type 2 diabetes.

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“…Many other Parkin-independent mechanisms, including receptor-mediated mechanisms, exist. For example, FUNDC1, an OMM-localized protein, can initiate mitophagy by recruiting the MAP1LC3B/LC3B through its LIR motif in mammalian cells [ 47 ]. The FUNDC1 activity is modulated by phosphorylation via several different kinases [ 48 ].…”

Section: Additional Parkin-independent Mitophagymentioning

confidence: 99%

Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases

Luan

et al. 2021

Oxidative Medicine and Cellular Longevity

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The normal function of the mitochondria is crucial for most tissues especially for those that demand a high energy supply. Emerging evidence has pointed out that healthy mitochondrial function is closely associated with normal heart function. When these processes fail to repair the damaged mitochondria, cells initiate a removal process referred to as mitophagy to clear away defective mitochondria. In cardiomyocytes, mitophagy is closely associated with metabolic activity, cell differentiation, apoptosis, and other physiological processes involved in major phenotypic alterations. Mitophagy alterations may contribute to detrimental or beneficial effects in a multitude of cardiac diseases, indicating potential clinical insights after a close understanding of the mechanisms. Here, we discuss the current opinions of mitophagy in the progression of cardiac diseases, such as ischemic heart disease, diabetic cardiomyopathy, cardiac hypertrophy, heart failure, and arrhythmia, and focus on the key molecules and related pathways involved in the regulation of mitophagy. We also discuss recently reported approaches targeting mitophagy in the therapy of cardiac diseases.

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The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases

Cited by 38 publications

References 68 publications

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders

Mitophagy and mitochondrial dynamics in type 2 diabetes mellitus treatment

Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases

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