Erratum: PGC-1α controls mitochondrial biogenesis and dynamics in lead-induced neurotoxicity

Dabrowska, Aleksandra; Venero, Jose Luis Luis; Iwasawa, Ryota; Hankir, Mohammed-khair; Rahman, Sunniyat; Boobis, Alan R.; Hajji, Nabil

doi:10.18632/aging.100955

Cited by 4 publications

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“…In our study, we showed that the results of meldonium treatment, including the in vivo effects, were coupled to PGC-1α or its orthologue Spargel (srl) gene overexpression. We might explain the same normalization of mitochondrial dynamics by the increase of PGC-1α expression, which in turn induces a balanced expression of fusion/fission genes by binding to their promoters and implying its direct role in the regulation of mitochondrial dynamics (Dabrowska et al, 2016). Future studies should clarify whether PPARγ activation mediates the PGC-1α elevation induced by meldonium or is related to other PPAR-independent mechanisms.…”

Section: Meldonium Inhibits Endogenous Carnitine Synthesis and Carnitinementioning

confidence: 83%

Meldonium improves Huntington’s disease mitochondrial dysfunction by restoring peroxisome proliferator‐activated receptor γ coactivator 1α expression

Cristo

Finicelli

Digilio

et al. 2018

Journal Cellular Physiology

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Mitochondrial dysfunction seems to play a fundamental role in the pathogenesis of neurodegeneration in Huntington’s disease (HD). We assessed possible neuroprotective actions of meldonium, a small molecule affecting mitochondrial fuel metabolism, in in vitro and in vivo HD models. We found that meldonium was able to prevent cytotoxicity induced by serum deprivation, to reduce the accumulation of mutated huntingtin (mHtt) aggregates, and to upregulate the expression of peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) in mHTT‐expressing cells. The PGC‐1α increase was accompanied by the increment of mitochondrial mass and by the rebalancing of mitochondrial dynamics with a promotion of the mitochondrial fusion. Meldonium‐induced PGC‐1α significantly alleviated motor dysfunction and prolonged the survival of a transgenic HD Drosophila model in which mHtt expression in the nervous system led to progressive motor performance deficits. Our study strongly suggests that PGC‐1α, as a master coregulator of mitochondrial biogenesis, energy homeostasis, and antioxidant defense, is a potential therapeutic target in HD.

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Section: Meldonium Inhibits Endogenous Carnitine Synthesis and Carnitinementioning

confidence: 83%

Meldonium improves Huntington’s disease mitochondrial dysfunction by restoring peroxisome proliferator‐activated receptor γ coactivator 1α expression

Cristo

Finicelli

Digilio

et al. 2018

Journal Cellular Physiology

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“…On the contrary, exercise training improves heart function, decreases incidence of heart failure in both mammals and Drosophila , and reduces body and heart fat levels and heart fibrillation (Wen et al, 2018; Zheng et al, 2017). In addition, exercise increased muscle NAD + levels (Green et al, 1992; Koltai et al, 2010), and the increasing NAD + levels could activate transcriptional activity of PGC-1α in cells and increase mitochondrial density (Dabrowska et al, 2016; Lan et al, 2017). These results hinted that NAD + /dSIR2/ PGC-1α pathway activation may be one of key mechanisms that exercise improved heart function and prevented lipotoxic cardiomyopathy.…”

Section: Resultsmentioning

confidence: 99%

“…Some evidence suggests that Sir2 expression can alter the transcriptional activity of the mitochondrial biogenesis coactivator PGC-1α, and it catalyzes PGC-1α deacetylation both in vitro and in vivo . Overexpression of Sir2 deacetylase or increasing NAD + levels activate transcriptional activity of PGC-1α in neurons and increases mitochondrial density (Dabrowska et al, 2016; Lan et al, 2017). It has been reported the PGC-1α in fly heart is a key gene in regulating the formation of lipotoxic cardiomyopathy (Diop et al, 2015; Dumont et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

“…The dSir2 apparently regulates expression of genes involved in fat metabolism, and lack of Sir2 increases fat deposition under normal conditions and consequently impairs starvation survival capabilities of flies (Banerjee et al, 2012). It has been reported that the FOXO and PGC-1 α activity can be modulated by SIR2 deacetylation (Dabrowska et al, 2016; Lan et al, 2017), and these two factors are important to the formation of lipotoxic cardiomyopathy in Drosophila (Diop et al, 2015; Dumont et al, 2018). However, there is no direct evidence that cardiac Sir2 can regulate heart lipid metabolism via activating PGC-1 α activity in Drosophila .…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, exercise training alters extrinsic modulation of the heart and improves the intrinsic pump capacity of the heart in human, and it also improves quality of life of patients with chronic heart failure (Chrysohoou et al, 2014; Jackson, 2000; “Water exercise safe for troubled hearts”, 2011). In addition, exercise increased muscle NAD + levels (Green et al, 1992; Koltai et al, 2010) and increasing NAD + levels activates transcriptional activity of PGC-1α in neurons and increases mitochondrial density (Dabrowska et al, 2016; Lan et al, 2017). Therefore, these results suggest that NAD + /dSIR2/ PGC-1α pathway activation may be one of the key mechanisms in which exercise improves heart function and prevents lipotoxic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

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Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD+/dSIR2/PGC-1α pathway activation in old Drosophila

Wen

Zheng

et al. 2019

Biology Open

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Lipotoxic cardiomyopathy is caused by excessive lipid accumulation in myocardial cells and it is a form of cardiac dysfunction. Cardiac PGC-1α overexpression prevents lipotoxic cardiomyopathy induced by a high-fat diet (HFD). The level of NAD+ and Sir2 expression upregulate the transcriptional activity of PGC-1α. Exercise improves cardiac NAD+ level and PGC-1α activity. However, the relationship between exercise, NAD+/dSIR2/PGC-1α pathway and lipotoxic cardiomyopathy remains unknown. In this study, flies were fed a HFD and exercised. The heart dSir2 gene was specifically expressed or knocked down by UAS/hand-Gal4 system. The results showed that either a HFD or dSir2 knockdown remarkably increased cardiac TG level and dFAS expression, reduced heart fractional shortening and diastolic diameter, increased arrhythmia index, and decreased heart NAD+ level, dSIR2 protein, dSir2 and PGC-1α expression levels. Contrarily, either exercise or dSir2 overexpression remarkably reduced heart TG level, dFAS expression and arrhythmia index, and notably increased heart fractional shortening, diastolic diameter, NAD+ level, dSIR2 level, and heart dSir2 and PGC-1α expression. Therefore, we declared that exercise training could improve lipotoxic cardiomyopathy induced by a HFD or cardiac dSir2 knockdown in old Drosophila. The NAD+/dSIR2/PGC-1α pathway activation was an important molecular mechanism of exercise resistance against lipotoxic cardiomyopathy.

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Erratum: PGC-1α controls mitochondrial biogenesis and dynamics in lead-induced neurotoxicity

Abstract: Aging (Albany NY) 2015; 7(9): 629-647.

Cited by 4 publications

References 0 publications

Meldonium improves Huntington’s disease mitochondrial dysfunction by restoring peroxisome proliferator‐activated receptor γ coactivator 1α expression

Meldonium improves Huntington’s disease mitochondrial dysfunction by restoring peroxisome proliferator‐activated receptor γ coactivator 1α expression

Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD+/dSIR2/PGC-1α pathway activation in old Drosophila

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