Metformin modulates mitochondrial function and mitophagy in peripheral blood mononuclear cells from type 2 diabetic patients

Díaz-Pozo, Pedro; Canet, Francisco; Díaz-Morales, Noelia; Abad-Jiménez, Zaida; López‐Domènech, Sandra; Vezza, Teresa; Apostolova, Nadezda; Morillas, Carlos; Rocha, Milagros; Víctor, Víctor M.

doi:10.1016/j.redox.2022.102342

Cited by 41 publications

(32 citation statements)

References 39 publications

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“…Neutrophils and PBMCs were isolated from blood collected in EDTA tubes as described previously [ 13 ]. For neutrophils, 1.0 × 10 6 cells were resuspended in RPMI media supplemented with 10% v/v FBS (Biowest) and used for leukocyte-endothelium interaction assays.…”

Section: Methodsmentioning

confidence: 99%

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Mitochondrial redox impairment and enhanced autophagy in peripheral blood mononuclear cells from type 1 diabetic patients

Canet¹,

Díaz-Pozo²,

Luna-Marco³

et al. 2022

Redox Biology

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Section: Methodsmentioning

confidence: 99%

“…The whole blood of patients (500 μl) was processed as previously described [ 13 ]. The fluorochromes (Invitrogen) 2′,7′-Dichlorodihydrofluorescein diacetate (5 μM, DCFH) and Hydroethidine (5 μM, HE) were employed to measure total free radicals and superoxide content, respectively.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial redox impairment and enhanced autophagy in peripheral blood mononuclear cells from type 1 diabetic patients

Canet¹,

Díaz-Pozo²,

Luna-Marco³

et al. 2022

Redox Biology

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“…Spermidine treatment was found to induce both the mitophagy as well as biogenesis of mitochondria in aged mice heart cells (Messerer et al, 2023). Metformin, a drug used in treating T2D, has been found to enhance mitochondrial function by restoring, ETC., proteins and promoting mitophagy (de Maranon et al, 2022).…”

Section: Autophagy and Proteasomal Defects Associated With Parkinson ...mentioning

confidence: 99%

Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing

Jagtap

Kumar

Kinger

et al. 2023

Front. Cell Dev. Biol.

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The disturbance in mitochondrial functions and homeostasis are the major features of neuron degenerative conditions, like Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Alzheimer’s disease, along with protein misfolding. The aberrantly folded proteins are known to link with impaired mitochondrial pathways, further contributing to disease pathogenesis. Despite their central significance, the implications of mitochondrial homeostasis disruption on other organelles and cellular processes remain insufficiently explored. Here, we have reviewed the dysfunction in mitochondrial physiology, under neuron degenerating conditions. The disease misfolded proteins impact quality control mechanisms of mitochondria, such as fission, fusion, mitophagy, and proteasomal clearance, to the detriment of neuron. The adversely affected mitochondrial functional roles, like oxidative phosphorylation, calcium homeostasis, and biomolecule synthesis as well as its axes and contacts with endoplasmic reticulum and lysosomes are also discussed. Mitochondria sense and respond to multiple cytotoxic stress to make cell adapt and survive, though chronic dysfunction leads to cell death. Mitochondria and their proteins can be candidates for biomarkers and therapeutic targets. Investigation of internetworking between mitochondria and neurodegeneration proteins can enhance our holistic understanding of such conditions and help in designing more targeted therapies.

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“…Pharmacological concentrations of metformin improve diverse parameters of mitochondrial function through AMPK action in a cell model of T2D hepatocytes and in liver tissue from HFD-T2D mice . In addition, in peripheral blood from T2D diabetic patients, metformin reduces mitochondrial ROS (mtROS) production, boosts the antioxidant response, prevents pro-fission mitochondrial morphology and induces an increase in mitophagy, possibly through AMPK action (de Marañón et al, 2022(de Marañón et al, , 2021. Similarly, in adipose tissue, metformin reduces the pro-fission phenotype in a AMP-activated protein kinase (AMPK)-dependent manner (Li et al, 2016).…”

Section: ) Introductionmentioning

confidence: 99%

Targeting mitochondria: a great boon to fight type 2 diabetes

Rovira‐Llopis

Rocha

Víctor

2022

Redox Experimental Medicine

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Type 2 diabetes is a chronic metabolic disease characterised by the development of low-grade systemic inflammation, hyperglycaemia, and hyperlipidaemia. These pathogenic traits have a profound impact on mitochondrial function as the intermediary organelles between nutrients and energy production. Moreover, the mitochondrial quality control system is also altered and rendered defective by type 2 diabetes. These alterations entail the accumulation of defective mitochondria, which causes the diabetic background to deteriorate further. In this context, it is of paramount importance to improve mitochondrial function and ameliorate the consequences of mitochondrial dysfunction. This review assesses different treatments that target mitochondrial dysfunction as a way of treating type 2 diabetes. Lifestyle interventions and pharmacological treatments such as biguanides, thiazolidinediones, a-glucosidase inhibitors or SGLT2 inhibitors protect mitochondrial function; while novel mitochondria-targeted molecules including natural compounds, mitochondria-targeted antioxidants, inhibitors of mPTP opening, NO and H2S donors, and inhibitors of mitochondrial fission positively impact on mitochondrial function and its quality control mechanisms. Most of these therapeutic tools require more research, but they already show promising therapeutic mechanisms that improve type 2 diabetes and its cellular consequences.

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Metformin modulates mitochondrial function and mitophagy in peripheral blood mononuclear cells from type 2 diabetic patients

Cited by 41 publications

References 39 publications

Mitochondrial redox impairment and enhanced autophagy in peripheral blood mononuclear cells from type 1 diabetic patients

Mitochondrial redox impairment and enhanced autophagy in peripheral blood mononuclear cells from type 1 diabetic patients

Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing

Targeting mitochondria: a great boon to fight type 2 diabetes

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