The Membrane-Bound - and -Lactate Dehydrogenase Activities in Mitochondria from Euglena gracilis

Jasso‐Chávez, Ricardo; Torres-Márquez, M. Eugenia; Moreno‐Sánchez, Rafael

doi:10.1006/abbi.2001.2353

Cited by 24 publications

(21 citation statements)

References 41 publications

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“…The presence of AOX was confirmed in silico (Perez et al 2014) and in vivo (Krnáčová et al 2015). Another pathway includes lactate dehydrogenase, which transfers electrons from lactate directly to ubiquinone (Moreno-Sánchez et al 2000) and is part of the lactate/pyruvate shuttle (Jasso-Chávez et al 2001Jasso-Chávez and Moreno-Sánchez 2003). Alternative respiratory pathways are likely involved in cellular responses to oxidative stress (Castro-Guerrero et al 2004, since E. gracilis lacks catalase, but contains ascorbate peroxidase (APX), which localizes exclusively to the cytosol (Shigeoka et al 2002).…”

Section: Aerobic Metabolic Pathwaymentioning

confidence: 73%

The Mitochondrion of Euglena gracilis

Zimorski

Rauch

Hellemond

et al. 2017

Advances in Experimental Medicine and Biology

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In the presence of oxygen, Euglena gracilis mitochondria function much like mammalian mitochondria. Under anaerobiosis, E. gracilis mitochondria perform a malonyl-CoA independent synthesis of fatty acids leading to accumulation of wax esters, which serve as the sink for electrons stemming from glycolytic ATP synthesis and pyruvate oxidation. Some components (enzymes and cofactors) of Euglena's anaerobic energy metabolism are found among the anaerobic mitochondria of invertebrates, others are found among hydrogenosomes, the H-producing anaerobic mitochondria of protists.

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Section: Aerobic Metabolic Pathwaymentioning

confidence: 73%

The Mitochondrion of Euglena gracilis

Zimorski

Rauch

Hellemond

et al. 2017

Advances in Experimental Medicine and Biology

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“…Because the genomic sequence of E. gracilis has not been determined, the number of lactate dehydrogenases is unknown. The activity of L -lactate and D -lactate dehydrogenase has been shown in the mitochondria and cytosol of E. gracilis (Jasso-Chávez et al, 2001, 2005). Thus, the production of both isomers using E. gracilis is rational; nevertheless the physiological relevance requires further examination.…”

Section: Discussionmentioning

confidence: 99%

Succinate and Lactate Production from Euglena gracilis during Dark, Anaerobic Conditions

et al. 2016

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Euglena gracilis is a eukaryotic, unicellular phytoflagellate that has been widely studied in basic science and applied science. Under dark, anaerobic conditions, the cells of E. gracilis produce a wax ester that can be converted into biofuel. Here, we demonstrate that under dark, anaerobic conditions, E. gracilis excretes organic acids, such as succinate and lactate, which are bulk chemicals used in the production of bioplastics. The levels of succinate were altered by changes in the medium and temperature during dark, anaerobic incubation. Succinate production was enhanced when cells were incubated in CM medium in the presence of NaHCO3. Excretion of lactate was minimal in the absence of external carbon sources, but lactate was produced in the presence of glucose during dark, anaerobic incubation. E. gracilis predominantly produced L-lactate; however, the percentage of D-lactate increased to 28.4% in CM medium at 30°C. Finally, we used a commercial strain of E. gracilis for succinate production and found that nitrogen-starved cells, incubated under dark, anaerobic conditions, produced 869.6 mg/L succinate over a 3-day incubation period, which was 70-fold higher than the amount produced by nitrogen-replete cells. This is the first study to demonstrate organic acid excretion by E. gracilis cells and to reveal novel aspects of primary carbon metabolism in this organism.

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“…The supernatant was then centrifuged at 105,000 ϫ g for 40 min at 4°C. The pellet was resuspended in the SHE medium plus 1% (w/v) fatty acidfree BSA and stored at Ϫ70°C until use (33).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Targeting of Vitamin E Succinate Enhances Its Pro-apoptotic and Anti-cancer Activity via Mitochondrial Complex II

Dong¹,

Jameson

Tilly

et al. 2011

Journal of Biological Chemistry

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186

192

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Mitochondrial complex II (CII) has been recently identified as a novel target for anti-cancer drugs. Mitochondrially targeted vitamin E succinate (MitoVES) is modified so that it is preferentially localized to mitochondria, greatly enhancing its pro-apoptotic and anti-cancer activity. Using genetically manipulated cells, MitoVES caused apoptosis and generation of reactive oxygen species (ROS) in CII-proficient malignant cells but not their CII-dysfunctional counterparts. MitoVES inhib-ited the succinate dehydrogenase (SDH) activity of CII with IC 50 of 80 M, whereas the electron transfer from CII to CIII was inhibited with IC 50 of 1.5 M. The agent had no effect either on the enzymatic activity of CI or on electron transfer from CI to CIII. Over 24 h, MitoVES caused stabilization of the oxygen-dependent destruction domain of HIF1␣ fused to GFP, indicating promotion of the state of pseudohypoxia. Molecular modeling predicted the succinyl group anchored into the proximal CII ubiquinone (UbQ)-binding site and successively reduced interaction energies for serially shorter phytyl chain homologs of MitoVES correlated with their lower effects on apoptosis induction, ROS generation, and SDH activity. Mutation of the UbQ-binding Ser 68 within the proximal site of the CII SDHC subunit (S68A or S68L) suppressed both ROS generation and apoptosis induction by MitoVES. In vivo studies indicated that MitoVES also acts by causing pseudohypoxia in the context of tumor suppression. We propose that mitochondrial targeting of VES with an 11-carbon chain localizes the agent into an ideal position across the interface of the mitochondrial inner membrane and matrix, optimizing its biological effects as an anti-cancer drug.Mitochondria are emerging as targets for a variety of anti-cancer drugs (1-5) that belong to a group of compounds termed "mitocans" (6, 7). Of these agents, we and others have been studying the group of vitamin E (VE) 2 analogs, epitomized by the "redox-silent" ␣-tocopheryl succinate (␣-TOS) and ␣-tocopheryl acetyl ether (8). Both of these agents proved to be selective inducers of apoptosis in cancer cells and efficient suppressors of tumors in experimental models (9 -16).VE analogs with anti-cancer activity have been classified as mitocans (i.e. small anti-cancer agents that act by selectively destabilizing mitochondria in cancer cells) (6 -8). Of the several groups of mitocans, the anti-cancer VE analogs belong to both the class of BH3 mimetics, which includes compounds interfering with the interactions of the Bcl-2 family proteins (17), as well as to the class of agents that interfere with the mitochondrial electron redox chain. The latter activity is probably the main reason for the strong apoptogenic efficacy of agents like ␣-TOS (18). More specifically, ␣-TOS interferes * This work was supported by grants from the Australian Research Council,

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The Membrane-Bound - and -Lactate Dehydrogenase Activities in Mitochondria from Euglena gracilis

Cited by 24 publications

References 41 publications

The Mitochondrion of Euglena gracilis

The Mitochondrion of Euglena gracilis

Succinate and Lactate Production from Euglena gracilis during Dark, Anaerobic Conditions

Mitochondrial Targeting of Vitamin E Succinate Enhances Its Pro-apoptotic and Anti-cancer Activity via Mitochondrial Complex II

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