Substrate- and Calcium-Dependent Differential Regulation of Mitochondrial Oxidative Phosphorylation and Energy Production in the Heart and Kidney

Zhang, Xiao; Tomar, Namrata; Kandel, Sunil M.; Audi, Said H.; Cowley, Allen W.; Dash, Ranjan K.

doi:10.3390/cells11010131

Cited by 15 publications

(11 citation statements)

References 121 publications

(219 reference statements)

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“…3 ). In line with this, recent results ( 36 ) show that isolated heart and kidney mitochondria exposed to pyruvate plus malate or α-KG plus malate have increased RCRs when in the presence of small increases in Ca 2+ concentrations (in the nanomolar range) but have decreased RCRs when Ca 2+ was further augmented. In contrast, Ca 2+ addition to isolated brain mitochondria energized by pyruvate plus malate leads to reduced RCRs, in a concentration-dependent manner, with no effect on PDH activity ( 37 ).…”

Section: Discussionsupporting

confidence: 73%

Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right

Vilas-Boas

Cabral-Costa

Ramos

et al. 2023

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 73%

Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right

Vilas-Boas

Cabral-Costa

Ramos

et al. 2023

Journal of Biological Chemistry

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“…3). In line with this, recent results (36) show that isolated heart and kidney mitochondria exposed to pyruvate plus malate or α-ketoglutarate plus malate have increased RCRs when in the presence of small increases in Ca 2+ concentrations (in the nanomolar range), but had decreased RCRs when Ca 2+ was further augmented. In contrast, Ca 2+ addition to isolated brain mitochondria energized by pyruvate plus malate leads to reduced RCRs, in a concentration-dependent manner, with no effect on PDH activity (37).…”

Section: Discussionsupporting

confidence: 73%

Goldilocks calcium and the mitochondrial respiratory chain: too much, too little, just right

Vilas-Boas

Cabral-Costa

Ramos

et al. 2022

Preprint

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Calcium (Ca2+) is a key regulator in diverse intracellular signaling pathways, and has long been implicated in metabolic control and mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important intracellular Ca2+ buffers and affecting cytosolic Ca2+ transients. Excessive mitochondrial matrix Ca2+ is known to be deleterious due to opening of the mitochondrial permeability transition pore (mPTP) and consequent membrane potential dissipation, leading to mitochondrial swelling, rupture and cell death. But moderate Ca2+ within the organelle can directly or indirectly activate mitochondrial matrix enzymes, possibly impacting on ATP production. However, in vitro studies involving the regulation of mitochondrial enzymes by Ca2+ may not uncover its full effects on oxidative phosphorylation. Here, we aimed to determine if extra or intramitochondrial Ca2+ modulate oxidative phosphorylation in mouse liver mitochondria and intact hepatocytes. We found that isolated mitochondria present increased respiratory control ratios (a measure of oxidative phosphorylation efficiency) when incubated with low and medium Ca2+ concentrations in the presence of complex I-linked substrates pyruvate plus malate and a-ketoglutarate, respectively, but not complex II-linked succinate. In intact hepatocytes, both low and high cytosolic Ca2+ led to decreased respiratory rates, while ideal rates were present under physiological conditions. High Ca2+ decreased mitochondrial respiration in cells in a substrate-dependent manner, mediated by mPTP. Overall, our results uncover a Goldilocks effect of Ca2+ on liver mitochondria, with specific 'just right' concentrations that activate oxidative phosphorylation.

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“…The OGDC consists of three enzymes: oxoglutarate dehydrogenase (EC 1.2.4.2; OGDH), dihydrolipoyl succinyltransferase (EC 2.3.1.61; DLST), and the previously mentioned DLD (EC 1.8.1.4). Diaz and Komuniecki [86] showed that the enzyme from F. hepatica is not upregulated by calcium ions, in contrast to the mammalian OGDH [87,88]. This issue also needs further investigation from the point of view of the effect of inhibitory substances on OGDH to kill helminths.…”

Section: Discussionmentioning

confidence: 99%

Tandem Mass Tagging (TMT) Reveals Tissue-Specific Proteome of L4 Larvae of Anisakis simplex s. s.: Enzymes of Energy and/or Carbohydrate Metabolism as Potential Drug Targets in Anisakiasis

Stryiński

Mateos

Carrera

et al. 2022

IJMS

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Anisakis simplex s. s. is a parasitic nematode of marine mammals and causative agent of anisakiasis in humans. The cuticle and intestine of the larvae are the tissues most responsible for direct and indirect contact, respectively, of the parasite with the host. At the L4 larval stage, tissues, such as the cuticle and intestine, are fully developed and functional, in contrast to the L3 stage. As such, this work provides for the first time the tissue-specific proteome of A. simplex s. s. larvae in the L4 stage. Statistical analysis (FC ≥ 2; p-value ≤ 0.01) showed that 107 proteins were differentially regulated (DRPs) between the cuticle and the rest of the larval body. In the comparison between the intestine and the rest of the larval body at the L4 stage, 123 proteins were identified as DRPs. Comparison of the individual tissues examined revealed a total of 272 DRPs, with 133 proteins more abundant in the cuticle and 139 proteins more abundant in the intestine. Detailed functional analysis of the identified proteins was performed using bioinformatics tools. Glycolysis and the tricarboxylic acid cycle were the most enriched metabolic pathways by cuticular and intestinal proteins, respectively, in the L4 stage of A. simplex s. s. The presence of two proteins, folliculin (FLCN) and oxoglutarate dehydrogenase (OGDH), was confirmed by Western blot, and their tertiary structure was predicted and compared with other species. In addition, host–pathogen interactions were identified, and potential new allergens were predicted. The result of this manuscript shows the largest number of protein identifications to our knowledge using proteomics tools for different tissues of L4 larvae of A. simplex s. s. The identified tissue-specific proteins could serve as targets for new drugs against anisakiasis.

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Substrate- and Calcium-Dependent Differential Regulation of Mitochondrial Oxidative Phosphorylation and Energy Production in the Heart and Kidney

Cited by 15 publications

References 121 publications

Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right

Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right

Goldilocks calcium and the mitochondrial respiratory chain: too much, too little, just right

Tandem Mass Tagging (TMT) Reveals Tissue-Specific Proteome of L4 Larvae of Anisakis simplex s. s.: Enzymes of Energy and/or Carbohydrate Metabolism as Potential Drug Targets in Anisakiasis

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