Extramitochondrial energy production in platelets

Ravera, Silvia; Signorello, Maria Grazia; Bartolucci, Martina; Ferrando, Sara; Manni, Lucia; Caicci, Federico; Calzia, Daniela; Panfoli, Isabella; Morelli, Alessandro; Leoncini, Giuliana

doi:10.1111/boc.201700025

Cited by 24 publications

(44 citation statements)

References 55 publications

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“…Since, in mitochondria, the proportion of these two proteins is conserved, this was considered a clue to the fact that ATP synthase could be also expressed in the internal platelet membranes. In other words, our study suggested the existence of an extramitochondrial energy production in platelets [18] [ Figure 1]. This hypothesis is confirmed by the confocal microscopy analysis, which shows a low signal of TIM in the face of a strong colocalization between COXII or β subunit of ATP synthase with calnexin, a marker of the endoplasmic reticulum (ER).…”

Section: New Perspectives On Oxidative Metabolism In Plateletssupporting

confidence: 78%

“…We have recently shown that platelets display a consistent oxygen consumption and ATP production in the presence of NADH, a respiring substrate not suitable for mitochondria in vitro. This NADH-stimulated oxygen consumption appeared sensitive to thrombin or collagen and insensitive to atractyloside, an inhibitor of Adenine nucleotide translocase [18] , suggesting that other structures are involved in platelets respiration besides mitochondria. Moreover, in platelets, the ratio of the expression of F 1 F o -ATP synthase and the translocase of the inner membrane (TIM; a mitochondrial inner membrane protein not involved in the OXPHOS) was higher than in mitochondria [18] .…”

Section: New Perspectives On Oxidative Metabolism In Plateletsmentioning

confidence: 94%

“…This NADH-stimulated oxygen consumption appeared sensitive to thrombin or collagen and insensitive to atractyloside, an inhibitor of Adenine nucleotide translocase [18] , suggesting that other structures are involved in platelets respiration besides mitochondria. Moreover, in platelets, the ratio of the expression of F 1 F o -ATP synthase and the translocase of the inner membrane (TIM; a mitochondrial inner membrane protein not involved in the OXPHOS) was higher than in mitochondria [18] . Since, in mitochondria, the proportion of these two proteins is conserved, this was considered a clue to the fact that ATP synthase could be also expressed in the internal platelet membranes.…”

Section: New Perspectives On Oxidative Metabolism In Plateletsmentioning

confidence: 94%

“…Although platelets metabolism is sustained by the OXPHOS, it seems that there is a mismatch among the platelet elevated aerobic metabolism and their mitochondria number [14,17] . We have recently shown, by TEM microscopy, that two is the average mitochondria number of platelets and several of them being devoid of mitochondria [18] . Notably, as far as the maturation process is involved, the number of platelets released per MK ranges from 2000-11,000 platelet per MK [2] .…”

Section: New Perspectives On Oxidative Metabolism In Plateletsmentioning

confidence: 96%

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Platelet aerobic metabolism: new perspectives

Ravera¹,

Panfoli²

2019

JUMD

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Although the role of platelets in hemostasis and thrombotic disorders as well as their contribution to inflammation are known, recent studies support the notion that much remains to be learned about platelet bioenergetics. Recent data suggest that platelets possess extra-mitochondrial oxidative phosphorylation (OXPHOS), which could represent one of sources of the chemical energy necessary for the prompt platelets activation. However, the extra-mitochondrial OXPHOS can play both beneficial and pathological roles, since the OXPHOS is the principal responsible of oxidative stress generation. For this reason, several authors evaluated the effects of polyphenols and other antioxidants on the modulation of the platelets oxidative stress production. In conclusion, we believe that a better understanding of platelet oxidative metabolism would allow a deeper knowledge of their physiology and the designing novel treatments targeting the role of platelets in many human diseases.

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Section: New Perspectives On Oxidative Metabolism In Plateletssupporting

confidence: 78%

Section: New Perspectives On Oxidative Metabolism In Plateletsmentioning

confidence: 94%

Section: New Perspectives On Oxidative Metabolism In Plateletsmentioning

confidence: 94%

Section: New Perspectives On Oxidative Metabolism In Plateletsmentioning

confidence: 96%

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Platelet aerobic metabolism: new perspectives

Ravera¹,

Panfoli²

2019

JUMD

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“…Platelets are attractive source of viable mitochondria, which can be obtained much less invasivelly compared to skeletal muscel biopsy (13,14). Platelets as circulating anucleate fragments, contain a small amount of mitochondria, important for energy production (15). Platelets are metabolically active cells with high energy consumption.…”

Section: Introductionmentioning

confidence: 99%

Platelet mitochondrial bioenergetic analysis in patients with nephropathies and non-communicable diseases: a new method

Gvozdjáková¹,

Sumbalová²,

Kucharská³

et al. 2019

BLL

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OBJECTIVES: To test the hypothesis if mitochondrial bioenergetic function analyzed in circulating platelets may represent peripheral signature of mitochondrial dysfunction in nephropathy associated to noncommunicable human diseases such as cardiovascular diseases, diabetes and with statins treatment. METHODS: High-resolution respirometry was used for analysis of mitochondrial bioenergetics in human platelets isolated from peripheral blood. This method is less-invasively compared to skeletal muscle biopsy. Patients with nephropathies and in combination with non-communicable diseases were included in the study. RESULTS: This pilot study showed platelet mitochondrial bioenergy dysfunction in patients with nephropathies and non-communicable diseases. Positive effect of treatment with 10 mg atorvastatin on platelet mitochondrial respiratory chain Complex I-linked respiration and ATP production in patients with nephropathies, diabetes and 80 mg atorvastatin in patient with nephropathy and dialysis was found. Positive effect of 80 mg fl uvastatin treatment, and negative effect of thrombocytopenia and renal transplantation on platelet mitochondrial bioenergy was determined. CONCLUSION: High-resolution respirometry allowed detection of small changes in platelet mitochondrial function. This method could be used as a sensitive bioenergetic test of mitochondrial function for diagnosis and monitoring the therapy in patients with nephropathy (Tab. 1, Fig. 3, Ref. 39). Text in PDF www.elis.sk.

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Endocannabinoids effect on oxidative status of human platelets

Signorello

Ravera

Leoncini

2022

J of Cellular Biochemistry

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Reactive oxygen species (ROS) are known to regulate platelet activation. Since endocannabinoids behave as platelet agonists, we investigated the effect of two endocannabinoids, 2-arachidonoylglycerol (2AG) and anandamide (AEA) on the oxidative status of human platelets. We have demonstrated that 2AG and AEA stimulate ROS production, superoxide anion formation and lipid peroxidation.The effect is dose and time dependent and mainly occurs through the involvement of cannabinoid receptor 1 (CB1) since all tested parameters are greatly reduced by SR141716, the CB1 specific inhibitor. The specific inhibitor of cannabinoid receptor 2 (CB2) SR144528 produces a very small inhibition. The involvement of syk/PI3K/AKT/mTor pathway in oxidative stress induced by endocannabinoids is shown. Nicotinamide adenine dinucleotide phosphate oxidase seems to be poorly involved in the endocannabinoids effect. Concerning the aerobic metabolism, it has been demonstrated that endocannabinoids reduce the oxygen consumption and adenosine triphosphate synthesis, both in the presence of pyruvate + malate or succinate. In addition, endocannabinoids inhibit the activity of respiratory complexes II, III and IV and increase the activity of respiratory complex I. The endocannabinoids effect on aerobic metabolism seems to be also a CB1 mediated mechanism. Thus, in human platelets oxidative stress induced by endocannabinoids, mainly generated in the respiratory chain through the activation of complex I and the inhibition of complex II, III and IV, may lead to thrombotic events, contributing to cardiovascular diseases.

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Extramitochondrial energy production in platelets

Abstract: This work represents a further example of the existence of an extramitochondrial aerobic metabolism, which can contribute to the cellular energy balance.

Cited by 24 publications

References 55 publications

Platelet aerobic metabolism: new perspectives

Platelet aerobic metabolism: new perspectives

Platelet mitochondrial bioenergetic analysis in patients with nephropathies and non-communicable diseases: a new method

Endocannabinoids effect on oxidative status of human platelets

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