Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis

2021 ◽  
Author(s):  
Yi-Ping Wang ◽  
Azeem Sharda ◽  
Shuang-Nian Xu ◽  
Nick van Gastel ◽  
Cheuk Him Man ◽  
...  
Author(s):  
Adriana Pérez ◽  
María Angélica Rivoira ◽  
Valeria Rodríguez ◽  
Ana Marchionatti ◽  
Nori Tolosa de Talamoni

Sodium deoxycholate (NaDOC) inhibits the intestinal Ca2+ absorption and ursodeoxycholic acid (UDCA) stimulates it. The aim of this study was to determine whether NaDOC and UDCA produce differential effects on the redox state of duodenal mitochondria altering the Krebs cycle and the electron transport chain (ETC) functioning, which could lead to perturbations in the mitochondrial dynamics and biogenesis. Rat intestinal mitochondria were isolated from untreated and treated animals with either NaDOC, UDCA, or both. Krebs cycle enzymes, ETC components, ATP synthase, and mitochondrial dynamics and biogenesis markers were determined. NaDOC decreased isocitrate dehydrogenase (ICDH) and malate dehydrogenase activities affecting the ETC and ATP synthesis. NaDOC also induced oxidative stress and increased the superoxide dismutase activity and impaired the mitochondrial biogenesis and functionality. UDCA increased the activities of ICDH and complex II of ETC. The combination of both bile acids conserved the functional activities of Krebs cycle enzymes, ETC components, oxidative phosphorylation, and mitochondrial biogenesis. In conclusion, the inhibitory effect of NaDOC on intestinal Ca2+ absorption is mediated by mitochondrial dysfunction, which is avoided by UDCA. The stimulatory effect of UDCA alone is associated with amelioration of mitochondrial functioning. This knowledge could improve treatment of diseases that affect the intestinal Ca2+ absorption.


HortScience ◽  
1994 ◽  
Vol 29 (5) ◽  
pp. 468f-468
Author(s):  
Ann M. Callahan ◽  
Carole L. Bassett

NADP-dependent Malic Enzyme (NADP-ME, EC 1.1.1.40) catalyzes the decarboxylation of malate, resulting in the release of CO2. In C3 plants the enzyme does not contribute CO2 directly to photosynthesis. Rather, it is associated with the supplemental synthesis of glycolytic and Krebs Cycle intermediates, although it may also be involved in regulating intracellular pH. NADP-ME activity increases during ripening of several fruits e.g. tomato and apple, usually in association with increased respiration of the developing fruit. We examined expression of NADP-ME during ripening in peach using a cDNA probe derived from F. trinervia (C4 dicot). The probe hybridized to a single RNA species of the predicted size and was low in abundance as expected for a C3 NADP-ME. As fruit matured, the RNA levels increased to a maximum around 133-140 days after bloom (fully ripe). NADP-ME RNA was not detectable from leaves isolated at the same time.


2020 ◽  
Vol 27 (SP2) ◽  
pp. e12-e21
Author(s):  
Laura Tedesco ◽  
Fabio Rossi ◽  
Chiara Ruocco ◽  
Maurizio Ragni ◽  
Michele O. Carruba ◽  
...  

Proper maintenance of mitochondrial homeostasis is essential for cell health, and mitochondrial dysfunction underlies several metabolic and heart diseases. Stimulation of mitochondrial biogenesis represents a valuable therapeutic tool for the prevention and treatment of disorders characterized by a deficit in energy metabolism. The present study aimed to potentiate the mitochondrial biogenetic efficacy of an amino acid (AA) mixture, enriched in branched-chain amino acids (BCAAs), which we previously showed to boost mitochondrial biogenesis, leading to life span extension and reducing of muscle and liver damage. Hence, we designed and studied several innovative mixtures. Here, we report on two new AA formulas, α5 and E7, created on the BCAA-enriched amino acid mixture (BCAAem) template and enriched with Krebs cycle substrates, including succinate, malate, and citrate. Cardiomyocytes in culture exposed to either mixture showed increased mitochondrial DNA amount, mitochondrial biogenesis markers, and oxygen consump-tion. Furthermore, α5 and E7 also increased the expression of BCAA catabolic genes. Most importantly, all of these effects of α5 and E7 were more pronounced than those observed with BCAAem, confirming the higher mitochondrial biogenesis potential of these new formulas. Therefore, α5 and E7 could represent a more efficient tool for the nutritional treatment of diseases in which energy production is defective.


Theories concerning the immediate origin of the increased rate of respiration at the climacteric in apples have been largely centred round an increase in mitochondrial activity (Hatch, Pearson, Millerd & Robertson 1959) probably because an increase in energy is required for synthetic processes occurring at this time (Pearson & Robertson 1954; Hulme 1954). Alternatively, it has been suggested (Millerd, Bonner & Biale 1953) that the close coupling between oxidation and phosphorylation in the mitochondrial system is destroyed during the climacteric period so that the respiration becomes uncontrolled. An improved method is used here for the isolation of mitochondria and soluble enzymes from apple tissue which obviates the inhibition of enzyme action by polyphenolic com pounds present in the tissue. The potential activity of isolated mitochondria increases over the climacteric, especially in the peel tissue, and the increase commences some days before any rise in CO 2 production of whole fruit is observed. In fruit detached from the tree before the climacteric has commenced, the climacteric is accompanied by a steep rise in the activity of malic enzyme and pyruvic carboxylase, particularly in the peel of fruit. After the climacteric peak, respiration rate and activity of malic enzyme and carboxylase fall, the changes running parallel particularly in the peel. The origin of the climacteric in fruit both ‘on’ and ‘off’ the tree, it is suggested, is due to an increase in activity — a synthesis, in fact— of malic enzyme and carboxylase, the source of energy for this synthesis being mitochondrial activity. This would also account for the increase in the respiratory quotient over the climacteric. The higher respiration rate of fruit at the climacteric peak on the tree (one-third more Co 2 production than in detached fruit) which is associated with a peculiar wateriness of the pulp, is due, it is claimed, to an increased permeability of the pulp tissue which allows a more rapid union between enzymes and substrates. The fall in respiration after the climacteric peak in storage (it has not been possible to follow post-climacteric changes in fruit on the tree) is attributed to a decrease in the activity of malic enzyme, carboxylase and the mitochondrial system operating the Krebs cycle; finally acid substrate becomes limiting. There is no evidence of an uncoupling, in the mitochondria, of oxidation and phosphorylation over the climacteric period.


Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5129
Author(s):  
Robert P. Walker ◽  
Zhi-Hui Chen ◽  
Franco Famiani

Gluconeogenesis is a key interface between organic acid/amino acid/lipid and sugar metabolism. The aims of this article are four-fold. First, to provide a concise overview of plant gluconeogenesis. Second, to emphasise the widespread occurrence of gluconeogenesis and its utilisation in diverse processes. Third, to stress the importance of the vacuolar storage and release of Krebs cycle acids/nitrogenous compounds, and of the role of gluconeogenesis and malic enzyme in this process. Fourth, to outline the contribution of fine control of enzyme activity to the coordinate-regulation of gluconeogenesis and malate metabolism, and the importance of cytosolic pH in this.


Author(s):  
S.M. Geyer ◽  
C.L. Mendenhall ◽  
J.T. Hung ◽  
E.L. Cardell ◽  
R.L. Drake ◽  
...  

Thirty-three mature male Holtzman rats were randomly placed in 3 treatment groups: Controls (C); Ethanolics (E); and Wine drinkers (W). The animals were fed synthetic diets (Lieber type) with ethanol or wine substituted isocalorically for carbohydrates in the diet of E and W groups, respectively. W received a volume of wine which provided the same gram quantity of alcohol consumed by E. The animals were sacrificed by decapitation after 6 weeks and the livers processed for quantitative triglycerides (T3), proteins, malic enzyme activity (MEA), light microscopy (LM) and electron microscopy (EM). Morphometric analysis of randomly selected LM and EM micrographs was performed to determine organellar changes in centrilobular (CV) and periportal (PV) regions of the liver. This analysis (Table 1) showed that hepatocytes from E were larger than those in C and W groups. Smooth endoplasmic reticulum decreased in E and increased in W compared to C values.


1991 ◽  
Vol 81 (4) ◽  
pp. 462-466 ◽  
Author(s):  
Maria Fabiana Drincovich ◽  
Alberto A. Iglesias ◽  
Carlos S. Andreo

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1966-P
Author(s):  
MENGISTU LEMECHA ◽  
KATSUTARO MORINO ◽  
TAKESHI IMAMURA ◽  
HIROTAKA IWASAKI ◽  
NATSUKO OHASHI ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document