Peroxisome-generated succinate induces lipid accumulation and oxidative stress in the kidneys of diabetic mice

Wang, Yaoqing; Zhang, Xiao; Yao, Haoya; Chen, Jiayao; Shang, Lin; Li, Ping; Cui, Xiaojuan; Zeng, Jia

doi:10.1016/j.jbc.2022.101660

Cited by 21 publications

(17 citation statements)

References 64 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this light, there is, perhaps, another relevant observation, and that is that in the kidneys of diabetic mice, peroxisomal succinate production is increased leading to increased lipid accumulation and oxidative stress via suppression of mitochondrial fatty acid oxidation [ 101 ]. It seems that succinate is a suppressor the antiviral immune response by modulating the MAVs complex [ 102 ].…”

Section: From Alkaline Vents To Mitochondria and Sars-cov-2mentioning

confidence: 99%

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Nunn

Guy²,

Brysch

et al. 2022

Biomedicines

View full text Add to dashboard Cite

Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as “brain fog”, fatigue and clotting problems. Explanations for “long COVID” include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can “tip” the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction. Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer’s metabolism needs to be “tipped” back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.

show abstract

Section: From Alkaline Vents To Mitochondria and Sars-cov-2mentioning

confidence: 99%

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Nunn

Guy²,

Brysch

et al. 2022

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Indeed, a peroxisome specific thioesterase (ACOT4) produces succinate out of the succinyl-CoA formed by the peroxisomal beta- or omega-oxidation of fatty acids [ 33 ], exiting the organelle possibly through the peroxisomal membrane protein 2 (PXMP2). Interestingly, it has been shown that this production of succinate by the peroxisome in response to an increase of free fatty acids (FFAs) could lead to an impairment of mitochondrial fatty acid β-oxidation through an increase of the NADH/NAD + ratio [ 34 ]. This succinate-mediated mitochondrial β-oxidation impairment could have implications in the naïve-to-primed ESC transition as this pathway has been shown to be upregulated in naïve ESCs [ 18 , 35 ] and in the ICM of pre-implantation blastocysts [ 36 ].…”

Section: Succinate As Metabolic Cross-roadsmentioning

confidence: 99%

“…This crosstalk between the PTMs could represent another way of regulating their deposition. Interestingly, most of the enzymes for the fatty acid oxidation in both peroxisomes and mitochondria were found to be succinylated but the resulting activity was opposite, activating in the peroxisome and inhibitory in the mitochondria [ 63 ], reminiscent of the inhibitory role of succinate on mitochondrial β-oxidation [ 34 ].…”

Section: Regulatory Roles Of Intracellular Succinatementioning

confidence: 99%

Succinate as a New Actor in Pluripotency and Early Development?

Detraux

Renard

2022

Metabolites

View full text Add to dashboard Cite

Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well as a small subpopulation of cells that have reacquired features of the 2C-embryo (2C-like cells) in naïve mouse ESC culture. Altogether, these represent a continuum of distinct pluripotency stages, characterized by metabolic transitions, for which we propose a new role for a long-known metabolite: succinate. Mostly seen as the metabolite of the TCA, succinate is also at the crossroad of several mitochondrial biochemical pathways. Its role also extends far beyond the mitochondrion, as it can be secreted, modify proteins by lysine succinylation and inhibit the activity of alpha-ketoglutarate-dependent dioxygenases, such as prolyl hydroxylase (PHDs) or histone and DNA demethylases. When released in the extracellular compartment, succinate can trigger several key transduction pathways after binding to SUCNR1, a G-Protein Coupled Receptor. In this review, we highlight the different intra- and extracellular roles that succinate might play in the fields of early pluripotency and embryo development.

show abstract

“…Some literatures pointed out that [17] The expression of Sirt3 and ROS production in HK-2 cells were decreased and the degree of apoptosis was increased in HK-2 cells induced by high glucose. A recent study showed that succinate produced by peroxisome in diabetic patients, as a pathological molecule, induces the accumulation of lipids and ROS in kidney and participates in the progression of DKD [18] .In summary, NADPH oxidase and mitochondrial electron transport chain, as the main sources of ROS, trigger various signaling pathways and activate some signaling molecules to cause irreversible pathological changes in cells and tissues, thus leading to renal function damage.…”

Section: Mitochondrial Oxidative Stress and Dkdmentioning

confidence: 99%

Progress in the correlation of mitochondrial dysfunction and diabetic kidney disease

2022

IJFM

View full text Add to dashboard Cite

Diabetic kidney disease(DKD) is the most common complication of diabetes prevalence rate increased year by year, kidney as one of the body organs consumption, need to provide enough mitochondria ATP to maintain the normal physiological function, sustained high blood sugar levels induced by activating multiple pathways mitochondria damage, cause the energy imbalance, ATP production, to its negative effects, in recent years, Mitochondrial dysfunction has been concerned in the occurrence and development of kidney diseases, and is considered to be a key factor involved in the pathogenesis of diabetic kidney disease. In this paper, the role of mitochondrial structure and dysfunction in the progression of DKD is described, providing a theoretical basis for controlling the progression of DKD.

show abstract

Peroxisome-generated succinate induces lipid accumulation and oxidative stress in the kidneys of diabetic mice

Cited by 21 publications

References 64 publications

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Succinate as a New Actor in Pluripotency and Early Development?

Progress in the correlation of mitochondrial dysfunction and diabetic kidney disease

Contact Info

Product

Resources

About