Mitochondrial Dysfunction and Mitophagy in Parkinson’s Disease: From Mechanism to Therapy

Malpartida, Ana Belen; Williamson, Matthew G; Narendra, Derek P.; Wade‐Martins, Richard; Ryan, Brent J.

doi:10.1016/j.tibs.2020.11.007

Cited by 301 publications

(241 citation statements)

References 109 publications

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“…To our knowledge, the most studied and understood mitophagy pathway is mediated by PTEN-induced kinase 1 (PINK1) and the E3 ubiquitin ligase Parkin (Narendra et al, 2008;Vives-Bauza et al, 2010), both of which have been linked to forms of Parkinson's disease (Kitada et al, 1998;Valente et al, 2004). The complicated mechanisms of canonical and non-canonical PINK1/parkinmediated mitophagy have been well summarized in previous reviews (Eiyama and Okamoto, 2015;Lazarou et al, 2015;Nguyen et al, 2016;Clark et al, 2020;Malpartida et al, 2020). Moreover, two main types of receptor-mediated mitophagy pathway have been classified as follows in brief: ubiquitinindependent mitophagy receptors, including BCL2-interacting protein 3 (BNIP3) (Quinsay et al, 2010), BCL2-interacting protein 3 like (NIX/BNIP3L) (Sandoval et al, 2008), FUN14 domain-containing 1 (FUNDC1) (Liu et al, 2012), BCL2-like 13 (BCL2L13) (Otsu et al, 2015), autophagy and beclin 1 regulator 1 (AMBRA1) (Strappazzon et al, 2015), FKBP prolyl isomerase 8 (FKBP8) (Bhujabal et al, 2017), prohibitin 2 (PHB2) (Wei et al, 2017), and NLR family member X1 (NLRX1) (Zhang et al, 2019); lipid-mediated mitophagy receptors, including ceramide (Sentelle et al, 2012) and cardiolipin (Li et al, 2015).…”

Section: Overview Of the Mitophagymentioning

confidence: 99%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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Mitochondrial function is multifaceted in response to cellular energy homeostasis and metabolism, with the generation of adenosine triphosphate (ATP) through the oxidative phosphorylation (OXPHOS) being one of their main functions. Selective elimination of mitochondria by mitophagy, in conjunction with mitochondrial biogenesis, regulates mitochondrial function that is required to meet metabolic demand or stress response. Growth hormone (GH) binds to the GH receptor (GHR) and induces the JAK2/STAT5 pathway to activate the synthesis of insulin-like growth factor 1 (IGF1). The GH–GHR–IGF1 axis has been recognized to play significant roles in somatic growth, including cell proliferation, differentiation, division, and survival. In this review, we describe recent discoveries providing evidence for the contribution of the GH–GHR–IGF1 axis on mitochondrial biogenesis, mitophagy (or autophagy), and mitochondrial function under multiple physiological conditions. This may further improve our understanding of the effects of the GH–GHR–IGF1 axis on mitochondrial function, which may be controlled by the delicate balance between mitochondrial biogenesis and mitophagy. Specifically, we also highlight the challenges that remain in this field.

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Section: Overview Of the Mitophagymentioning

confidence: 99%

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Zhang

2021

Front. Cell Dev. Biol.

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“…As the name of Parkin, this protein is widely known as the protein associated with PD. Neurodegeneration in PD is related to mitochondrial dysfunction, and recently, studies have shown that PINK1/Parkin-dependent mitophagy responding to mitochondrial damage is associated with PD (Malpartida et al, 2021). Besides, there has been a study on the pathogenesis of PD through the association between α-synuclein aggregation and neuroinflammation (Liu et al, 2019).…”

Section: Clinical Roles Of the Autophagic Organelles In Ddrs Molecular Pathology Of Ddr-related Autophagic Organellesmentioning

confidence: 99%

Autophagic Organelles in DNA Damage Response

Kim

Lee

Kim

et al. 2021

Front. Cell Dev. Biol.

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Autophagy is an important subcellular event engaged in the maintenance of cellular homeostasis via the degradation of cargo proteins and malfunctioning organelles. In response to cellular stresses, like nutrient deprivation, infection, and DNA damaging agents, autophagy is activated to reduce the damage and restore cellular homeostasis. One of the responses to cellular stresses is the DNA damage response (DDR), the intracellular pathway that senses and repairs damaged DNA. Proper regulation of these pathways is crucial for preventing diseases. The involvement of autophagy in the repair and elimination of DNA aberrations is essential for cell survival and recovery to normal conditions, highlighting the importance of autophagy in the resolution of cell fate. In this review, we summarized the latest information about autophagic recycling of mitochondria, endoplasmic reticulum (ER), and ribosomes (called mitophagy, ER-phagy, and ribophagy, respectively) in response to DNA damage. In addition, we have described the key events necessary for a comprehensive understanding of autophagy signaling networks. Finally, we have highlighted the importance of the autophagy activated by DDR and appropriate regulation of autophagic organelles, suggesting insights for future studies. Especially, DDR from DNA damaging agents including ionizing radiation (IR) or anti-cancer drugs, induces damage to subcellular organelles and autophagy is the key mechanism for removing impaired organelles.

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“…Systemic administration of the dopamine precursor L-3,4-dihydroxyphenylalanine (L-dopa) is the gold standard for PD treatment, and, over time, almost all PD patients require this pharmacological treatment [ 4 ]. Several pathophysiological mechanisms have been suggested to underlie the neurodegeneration of PD, including mitochondrial impairment, which seems to be an early event in PD [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial D-Loop Region Methylation and Copy Number in Peripheral Blood DNA of Parkinson’s Disease Patients

Stoccoro

Smith

Baldacci

et al. 2021

Genes

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Altered mitochondrial DNA (mtDNA) methylation has been detected in several human pathologies, although little attention has been given to neurodegenerative diseases. Recently, altered methylation levels of the mitochondrial displacement loop (D-loop) region, which regulates mtDNA replication, were observed in peripheral blood cells of Alzheimer’s disease and amyotrophic lateral sclerosis patients. However, nothing is yet known about D-loop region methylation levels in peripheral blood of Parkinson’s disease (PD) patients. In the current study, we investigated D-loop methylation levels and mtDNA copy number in peripheral blood of 30 PD patients and 30 age- and sex-matched control subjects. DNA methylation analyses have been performed by means of methylation-sensitive high-resolution melting (MS-HRM) and pyrosequencing techniques, while mtDNA copy number was analyzed by quantitative PCR. MS-HRM and pyrosequencing analyses provided very similar D-loop methylation levels in PD patients and control subjects, and no differences between the two groups have been observed. Treatment with L-dopa and duration of the disease had no effect on D-loop methylation levels in PD patients. Additionally, mtDNA copy number did not differ between PD patients and control subjects. Current results suggest that D-loop methylation levels are not altered in peripheral blood of PD patients nor influenced by dopaminergic treatment.

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Mitochondrial Dysfunction and Mitophagy in Parkinson’s Disease: From Mechanism to Therapy

Cited by 301 publications

References 109 publications

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

A Balanced Act: The Effects of GH–GHR–IGF1 Axis on Mitochondrial Function

Autophagic Organelles in DNA Damage Response

Mitochondrial D-Loop Region Methylation and Copy Number in Peripheral Blood DNA of Parkinson’s Disease Patients

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