Fatty acids as modulators of the cellular production of reactive oxygen species

Schönfeld, Peter; Wojtczak, Lech

doi:10.1016/j.freeradbiomed.2008.04.029

Cited by 381 publications

(293 citation statements)

References 178 publications

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“…by several mechanisms, such as interaction with components of the respiratory chain, thereby inhibiting the electron transport. 41 Our observation that PA significantly increased mitochondrial ROS and decreased mitochondrial membrane potential in autophagy-deficient PTCs, both of which could trigger mitophagy, 42 suggests that autophagy could be triggered to target dysfunctional mitochondria during lipid overload. Indeed, PA-induced mitophagy has been recently reported in human aortic endothelial cells.…”

Section: Discussionmentioning

confidence: 79%

High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney

Yamamoto¹,

Takabatake²,

Takahashi³

et al. 2016

JASN

198

194

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Excessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation. Pulse-chase experiments revealed that the accumulated lipids originated from cellular membranes. In mice with induced PTC-specific ablation of autophagy, PTCs of HFD-mice exhibited greater accumulation of ubiquitin-positive protein aggregates normally removed by autophagy than did PTCs of mice fed a normal diet. Furthermore, HFD-mice had no capacity to augment autophagic activity upon another pathologic stress. Autophagy ablation also exaggerated HFD-induced mitochondrial dysfunction and inflammasome activation. Moreover, renal ischemia-reperfusion induced greater injury in HFD-mice than in mice fed a normal diet, and ablation of autophagy further exacerbated this effect. Finally, we detected similarly enhanced phospholipid accumulation in enlarged lysosomes and impaired autophagic flux in the kidneys of obese patients compared with nonobese patients. These findings provide key insights regarding the pathophysiology of lipotoxicity in the kidney and clues to a novel treatment for obesity-related kidney diseases.

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Section: Discussionmentioning

confidence: 79%

High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney

Yamamoto¹,

Takabatake²,

Takahashi³

et al. 2016

JASN

198

194

View full text Add to dashboard Cite

show abstract

“…In potential, and thereby regulates cell death [29], and exogenous long chain free fatty acids (FFA) are reported to interfere with complex I and III in mitochondrial ETC [30].…”

Section: Discussionmentioning

confidence: 99%

Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells

et al. 2017

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“…Free fatty acids induce lipoapoptosis in hepatocytes and may impair FAO and cause hepatic damage (53,54). Nonesterified saturated free fatty acids, such as palmitate, are toxic to hepatocytes; thus, in Abcb11 deficiency, elevation of FFAs may pro- FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

Abcb11 Deficiency Induces Cholestasis Coupled to Impaired β-Fatty Acid Oxidation in Mice

Zhang

Patterson

et al. 2012

Journal of Biological Chemistry

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Fatty acids as modulators of the cellular production of reactive oxygen species

Cited by 381 publications

References 178 publications

High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney

High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney

Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells

Abcb11 Deficiency Induces Cholestasis Coupled to Impaired β-Fatty Acid Oxidation in Mice

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