Mitochondria elongation is mediated through SIRT1-mediated MFN1 stabilization

Oanh, Nguyen Thi Kim; Park, Yong-Yea; Cho, Hyeseong

doi:10.1016/j.cellsig.2017.06.019

Cited by 48 publications

(32 citation statements)

References 33 publications

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“…Notably, melatonin may directly reduce diabetic renal damage by sustaining mitochondrial homeostasis. This notion has been supported by ample evidence, which has documented the role of melatonin in mitochondrial protection (27,64,65). Melatonin suppresses excessive mitochondria fission (19), reverses protective mitophagy (24), scavenges mitochondrial ROS (66), alleviates mitochondrial calcium overload (18,67), sustains mitochondrial energy metabolism (68), modifies mitochondrial sirtuin protein (69) and blocks the caspase-9 apoptosis pathway (61,70).…”

Section: Discussionmentioning

confidence: 99%

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Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function

Yan

et al. 2018

Mol Med Report

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Mitochondrial homeostasis is a highly regulated process that serves a critical role in the maintenance of renal structure and function. The growing interest in the field of mitochondrial homeostasis promises to provide more information regarding the mechanisms involved in diabetic renal fibrosis, and aid in the development of novel strategies to combat the disease. In the present study, the effects of melatonin on renal damage in mice with diabetes were evaluated and the underlying mechanisms were investigated.

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Section: Discussionmentioning

confidence: 99%

“…Sample preparation and histological analysis. The kidneys were harvested, fixed for 1 h in 4% (w/v) paraformaldehyde at room temperature, and rapidly frozen in Optimal Cutting Temperature Compound (Agar Scientific, Ltd., Stansted, UK) for the preparation of cryosections (size, 4 µm) (27). Hematoxylin and eosin (H&E), Masson's trichrome (cat.…”

Section: Methodsmentioning

confidence: 99%

Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function

Yan

et al. 2018

Mol Med Report

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“…Scientific, Inc.) according to the manufacturer's protocol (Oanh, Park, & Cho, 2017). Null vector transfection was used as the control group (Ad-ctrl).…”

Section: Mem Media Supplemented With Lipofectamine 2000 (Thermo Fishermentioning

confidence: 99%

DUSP1 recuses diabetic nephropathy via repressing JNK‐Mff‐mitochondrial fission pathways

Sheng

Dai

et al. 2018

Journal Cellular Physiology

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Excessive mitochondrial fission has been identified as the pathogenesis of diabetic nephropathy (DN), although the upstream regulatory signal for mitochondrial fission activation in the setting of DN remains unknown. In the current study, we found that dual-specificity protein phosphatase-1 (DUSP1) was actually downregulated by chronic hyperglycemia stimulus. Lower DUSP1 expression was associated with glucose metabolism disorder, renal dysfunction, kidney hypertrophy, renal fibrosis, and glomerular apoptosis. At the molecular level, defective DUSP1 expression activated JNK pathway, and the latter selectively opened mitochondrial fission by modulating mitochondrial fission factor (Mff) phosphorylation. Excessive Mff-related mitochondrial fission evoked mitochondrial oxidative stress, promoted mPTP opening, exacerbated proapoptotic protein leakage into the cytoplasm, and finally initiated mitochondria-dependent cellular apoptosis in the setting of diabetes. However, overexpression of DUSP1 interrupted Mff-related mitochondrial fission, reducing hyperglycemia-mediated mitochondrial damage and thus improving renal function. Overall, we have shown that DUSP1 functions as a novel malefactor in diabetic renal damage that mediates via modifying Mff-related mitochondrial fission. Thus, finding strategies to regulate the balance of the DUSP1-JNK-Mff signaling pathway and mitochondrial homeostasis may be a therapeutic target for treating diabetic nephropathy in clinical practice.

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“…Transfection was carried out via incubating cells with siRNAs in Opti-MEM media supplemented with Lipofectamine® 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol [51]. Infection was performed for 48 h at 37˚C and infection efficiency was confirmed via western blotting.…”

Section: Rna Interferencementioning

confidence: 99%

NR4A1 Promotes Diabetic Nephropathy by Activating Mff-Mediated Mitochondrial Fission and Suppressing Parkin-Mediated Mitophagy

Sheng

Dai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Disrupted mitochondrial dynamics, including excessive mitochondrial fission and mitophagy arrest, has been identified as a pathogenic factor in diabetic nephropathy (DN), although the upstream regulatory signal for mitochondrial fission activation and mitophagy arrest in the setting of DN remains unknown. Methods: Wild-type (WT) mice and NR4A1 knockout (NR4A1-KO) mice were used to establish a DN model. Mitochondrial fission and mitophagy were evaluated by western blotting and immunofluorescence. Mitochondrial function was assessed by JC-1 staining, the mPTP opening assay, immunofluorescence and western blotting. Renal histopathology and morphometric analyses were conducted via H&E, Masson and PASM staining. Kidney function was evaluated via ELISA, western blotting and qPCR. Results: In the present study, we found that nuclear receptor subfamily 4 group A member 1 (NR4A1) was actually activated by a chronic hyperglycemic stimulus. Higher NR4A1 expression was associated with glucose metabolism disorder, renal dysfunction, kidney hypertrophy, renal fibrosis, and glomerular apoptosis. At the molecular level, increased NR4A1 expression activated p53, and the latter selectively stimulated mitochondrial fission and inhibited mitophagy by modulating Mff and Parkin transcription. Excessive Mff-related mitochondrial fission caused mitochondrial oxidative stress, promoted mPTP opening, exacerbated proapoptotic protein leakage into the cytoplasm, and finally initiated mitochondria-dependent cellular apoptosis in the setting of diabetes. In addition, defective Parkin-mediated mitophagy repressed cellular ATP production and failed to correct the uncontrolled mitochondrial fission. However, NR4A1 knockdown interrupted the Mff-related mitochondrial fission and recused Parkin-mediated mitophagy, reducing the hyperglycemia-mediated mitochondrial damage and thus improving renal function. Conclusion: Overall, we have shown that NR4A1 functions as a novel malefactor in diabetic renal damage and operates by synchronously enhancing Mff-related mitochondrial fission and repressing Parkin-mediated mitophagy. Thus, finding strategies to regulate the balance of the NR4A1-p53 signaling pathway and mitochondrial homeostasis may be a therapeutic option for treating diabetic nephropathy in clinical practice.

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Mitochondria elongation is mediated through SIRT1-mediated MFN1 stabilization

Cited by 48 publications

References 33 publications

Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function

Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function

DUSP1 recuses diabetic nephropathy via repressing JNK‐Mff‐mitochondrial fission pathways

NR4A1 Promotes Diabetic Nephropathy by Activating Mff-Mediated Mitochondrial Fission and Suppressing Parkin-Mediated Mitophagy

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