Intracellular Energy-Transfer Networks and High-Resolution Respirometry: A Convenient Approach for Studying Their Function

Puurand, Marju; Tepp, Kersti; Klepinin, Aleksandr; Klepinina, Lyudmila; Shevchuk, Igor; Käämbre, Tuuli

doi:10.3390/ijms19102933

Cited by 13 publications

(16 citation statements)

References 90 publications

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“…In the fully formed MI complex of the oxidative muscle cells, the interaction between βII-tubulin CTT and VDAC impedes adenine nucleotide movement through the channel and works as a switch, by which energy-rich phosphate is directed to the energy transport networks (Figure 1). The changes in tissue-specific diffusion restrictions for adenine nucleotides in the level of MOM can be easily characterized by measuring the apparent KmADP in permeabilized cells and tissues [88]. Furthermore, determination of MI composition and function in cardiac cells may provide opportunities for possible bioenergetic therapy associated with reinforcement of the binding of tubulin to VDAC to maintain the regulation of mitochondrial respiration via micro-compartmentalization of adenine nucleotides and the control of energy fluxes through MOM.…”

Section: Discussionmentioning

confidence: 99%

Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease

Puurand

Tepp

Timohhina

et al. 2019

Cells

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In recent decades, there have been several models describing the relationships between the cytoskeleton and the bioenergetic function of the cell. The main player in these models is the voltage-dependent anion channel (VDAC), located in the mitochondrial outer membrane. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. At the same time, high-energy phosphates are channeled out and directed to cellular energy transfer networks. Regulation of these energy fluxes is controlled by β-tubulin, bound to VDAC. It is also thought that β-tubulin‒VDAC interaction modulates cellular energy metabolism in cancer, e.g., switching from oxidative phosphorylation to glycolysis. In this review we focus on the described roles of unpolymerized αβ-tubulin heterodimers in regulating VDAC permeability for adenine nucleotides and cellular bioenergetics. We introduce the Mitochondrial Interactosome model and the function of the βII-tubulin subunit in this model in muscle cells and brain synaptosomes, and also consider the role of βIII-tubulin in cancer cells.

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Section: Discussionmentioning

confidence: 99%

Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease

Puurand

Tepp

Timohhina

et al. 2019

Cells

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“…To determine the apparent affinity of mitochondria to exogenous ADP (K m (ADP)), the dependence of respiration rate on exogenous ADP was measured ( Figure 3A). The obtained data were plotted as rates of O 2 consumption (the basal respiration rate of respiration was subtracted) versus ADP concentration and K m (ADP) and V max values were calculated from these plots by nonlinear regression using Michaelis-Menten equation [69,70] ( Figure 3B). Additionally, plotting the data to double reciprocal plot gives information about presence of different mitochondrial populations with differently regulated MOM.…”

Section: Oxygraphic Measurementsmentioning

confidence: 99%

Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps

Rebane-Klemm

Truu

Reinsalu

et al. 2020

Cancers

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This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry. ADP-activated respiration rate (Vmax) and an apparent affinity of mitochondria to ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower Vmax values compared to wild-type; however, the Vmax value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated polyps had higher Vmax values and elevated MOM permeability as compared to the control. BRAF mutated CRC and polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and polyps. Assessment of the tumor mitochondrial ATP synthesis could be a potential component of patient risk stratification.

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“…To first assess levels of metabolic activity in testicular tissue, we quantified mitochondrial oxygen consumption in situ using permeabilized testes cells. This recently developed technique quantifies mitochondrial function whilst preserving the organelle's morphology and physiological interactions within cells and offers insights into mitochondrial respiratory function in vivo (Picard et al, ; Puurand et al, ). To our knowledge, this is the first application of the tissue permeabilization metabolic estimation method in an insect.…”

Section: Methodsmentioning

confidence: 99%

Extreme variation in testes size in an insect is linked to recent mating activity

Greenway

Cirino

Wilner

et al. 2019

J of Evolutionary Biology

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Ample sperm production is essential for successful male reproduction in many species. The amount of sperm a male can produce is typically constrained by the size of his testes, which can be energetically expensive to grow and maintain. Although the economics of ejaculate allocation has been the focus of much theoretical and empirical literature, relatively little attention has been paid to individual adult variation and plasticity at the source of sperm production, the testes themselves. We experimentally address this issue using the insect Narnia femorata Stål (Hemiptera: Coreidae). We established the metabolic cost of testicular tissue and then quantified variation in individual testes mass in response to multiple mate quality and quantity treatments. We uncovered extreme variation across individuals and considerable short‐term effects of mating activity on testes dry mass. Importantly, the observed variation in testes mass was associated with notable fitness consequences; females paired with males with larger testes had greater hatching success. Overall, pairing with a female resulted in a 11% reduction in dry testes mass. Despite this apparent considerable mating investment, we found no evidence of strategic allocation to higher quality females or longer‐term changes in testes mass. The dynamic nature of testes mass and its metabolic cost is vital to consider in the context of re‐mating rates, polyandry benefits and general mating system dynamics both in this species and more broadly.

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Intracellular Energy-Transfer Networks and High-Resolution Respirometry: A Convenient Approach for Studying Their Function

Cited by 13 publications

References 90 publications

Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease

Tubulin βII and βIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease

Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps

Extreme variation in testes size in an insect is linked to recent mating activity

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