Effects of proton pumping on the structural rigidity of cristae in mitochondria

Yoneda, Mayu; Aklima, Jannatul; Ohsawa, Ikuroh; Ohta, Yoshihiro

doi:10.1016/j.abb.2022.109172

Cited by 5 publications

(7 citation statements)

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“…pH levels can also affect the deformability of mitochondria and their fission and fusion rates by perturbing the organization of the mitochondrial membranes (Wang et al., 2008; Gonzalez‐Rodriguez et al., 2015; Yoneda et al., 2022). A non‐physiological pH stiffens isolated mitochondria, as deduced from the deformation of these organelles using the micropipette aspiration technique (Wang et al., 2008).…”

Section: Mechanical Cues and Alterations In Mitochondrial Mechanical ...mentioning

confidence: 99%

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Villard

Manneville

2023

Biology of the Cell

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Metabolism and mechanics are two key facets of structural and functional processes in cells, such as growth, proliferation, homeostasis and regeneration. Their reciprocal regulation has been increasingly acknowledged in recent years: external physical and mechanical cues entail metabolic changes, which in return regulate cell mechanosensing and mechanotransduction. Since mitochondria are pivotal regulators of metabolism, we review here the reciprocal links between mitochondrial morphodynamics, mechanics and metabolism. Mitochondria are highly dynamic organelles which sense and integrate mechanical, physical and metabolic cues to adapt their morphology, the organization of their network and their metabolic functions. While some of the links between mitochondrial morphodynamics, mechanics and metabolism are already well established, others are still poorly documented and open new fields of research. First, cell metabolism is known to correlate with mitochondrial morphodynamics. For instance, mitochondrial fission, fusion and cristae remodeling allow the cell to fine‐tune its energy production through the contribution of mitochondrial oxidative phosphorylation and cytosolic glycolysis. Second, mechanical cues and alterations in mitochondrial mechanical properties reshape and reorganize the mitochondrial network. Mitochondrial membrane tension emerges as a decisive physical property which regulates mitochondrial morphodynamics. However, the converse link hypothesizing a contribution of morphodynamics to mitochondria mechanics and/or mechanosensitivity has not yet been demonstrated. Third, we highlight that mitochondrial mechanics and metabolism are reciprocally regulated, although little is known about the mechanical adaptation of mitochondria in response to metabolic cues. Deciphering the links between mitochondrial morphodynamics, mechanics and metabolism still presents significant technical and conceptual challenges but is crucial both for a better understanding of mechanobiology and for potential novel therapeutic approaches in diseases such as cancer.

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Section: Mechanical Cues and Alterations In Mitochondrial Mechanical ...mentioning

confidence: 99%

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Villard

Manneville

2023

Biology of the Cell

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“…Pantoprazole blocked the level of COX inducing the increased depolarized mitochondria (Δψ m) and ROS levels 149 . Moreover, PPIs, as the inhibitor of pump proton, have the potential of inhibiting the activity of mitochondrial electron transport complex, electron transport to reduce mitochondrial respiration and energy supplement so that promoting tumour cell death 192 …”

Section: Tumour Microenvironment Is the Main Medium For The Prolifera...mentioning

confidence: 99%

“…Besides, STAT3 plays an important role in maintaining and promoting the tumorigenic inflammatory environment, the transformation and progression of malignant tumours based on NF‐κB and IL‐6/GP130/JAK pathways 255 . There has been a research reporting that pantoprazole can inhibit the activity of the IL‐6/STAT3 pathway in gastric cancer cells 192 …”

Section: Tumour Microenvironment Is the Main Medium For The Prolifera...mentioning

confidence: 99%

“…149 Moreover, PPIs, as the inhibitor of pump proton, have the potential of inhibiting the activity of mitochondrial electron transport complex, electron transport to reduce mitochondrial respiration and energy supplement so that promoting tumour cell death. 192 Different PPIs own different mechanisms of inducing apoptosis.…”

Section: Ppis Can Induce Apoptosis By Changing the Anoxic Tumour Micr...mentioning

confidence: 99%

“…255 There has been a research reporting that pantoprazole can inhibit the activity of the IL-6/STAT3 pathway in gastric cancer cells. 192 TNF-α and IL-6 are two kinds of cytokines that play an important role in the process of cancerous cachexia. 256,257 IL-6-like cytokines independently mediate the excessive lipolysis and metabolism in cancerous cachexia.…”

Section: Ppis Can Inhibit Tumour Progression By Inhibiting Tumour-rel...mentioning

confidence: 99%

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Proton pump inhibitors display anti‐tumour potential in glioma

Rao

2022

Cell Proliferation

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Objectives: Glioma is one of the most aggressive brain tumours with poor overall survival despite advanced technology in surgical resection, chemotherapy and radiation.Progression and recurrence are the hinge causes of low survival. Our aim is to explain the concrete mechanism in the proliferation and progression of tumours based on tumour microenvironment (TME). The main purpose is to illustrate the mechanism of proton pump inhibitors (PPIs) in affecting acidity, hypoxia, oxidative stress, inflammatory response and autophagy based on the TME to induce apoptosis and enhance the sensitivity of chemoradiotherapy.Findings: TME is the main medium for tumour growth and progression. Acidity, hypoxia, inflammatory response, autophagy, angiogenesis and so on are the main causes of tumour progress. PPIs, as a common clinical drug to inhibit gastric acid secretion, have the advantages of fast onset, long action time and small adverse reactions.Nowadays, several kinds of literature highlight the potential of PPIs in inhibiting tumour progression. However, long-term use of PPIs alone also has obvious side effects. Therefore, till now, how to apply PPIs to promote the effect of radiochemotherapy and find the concrete dose and concentration of combined use are novel challenges.Conclusions: PPIs display the potential in enhancing the sensitivity of chemoradiotherapy to defend against glioma based on TME. In the clinic, it is also necessary to explore specific concentrations and dosages in synthetic applications. | BACKGROUNDGlioma is one of the most aggressive brain tumours. Histologically, the World Health Organization (WHO) classified the tumours of the central nervous system (CNS) into astrocytomas, oligodendrogliomas and ependymoma. In addition, gliomas are classified into four grades according to the degree of malignancy. Types I and II are low-grade gliomas and types III and IV are high-grade gliomas. [1][2][3] The clinical cure rate and 5-year survival rate of patients are all very low. The prognosis is very dismal and the average survival period is only about 1 year. One of the main reasons for the poor prognosis of patients is that glioma is prone to drug resistance to chemoradiation therapy resistance. 4,5 Therefore, it is urgent to explore new strategies for glioma treatment.Pump proton inhibitors (PPIs) are a drug of choice for inhibiting gastric acid secretion. In clinical, they are the first-line option to treat peptic ulcers, gastroesophageal reflux disease, zoai syndrome and upper gastrointestinal bleeding. 6,7 It has become the first-line drug for abnormal gastric acid secretion and related diseases combined with amoxicillin, clarithromycin and other drugs to treat Helicobacter pylori infection. 8,9 PPIs have the advantages of fast onset, strong acid inhibition, long action time, low blood drug concentration and low

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