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Malic enzyme

About: Malic enzyme is a research topic. Over the lifetime, 1761 publications have been published within this topic receiving 49883 citations.


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Journal ArticleDOI
31 Jan 2013-Nature
TL;DR: A new mechanism by which p53 represses the expression of the tricarboxylic-acid-cycle-associated malic enzymes ME1 and ME2 in human and mouse cells is described and a connection between metabolism and senescence mediated by p53 is revealed.
Abstract: Cellular senescence both protects multicellular organisms from cancer and contributes to their ageing The pre-eminent tumour suppressor p53 has an important role in the induction and maintenance of senescence, but how it carries out this function remains poorly understood In addition, although increasing evidence supports the idea that metabolic changes underlie many cell-fate decisions and p53-mediated tumour suppression, few connections between metabolic enzymes and senescence have been established Here we describe a new mechanism by which p53 links these functions We show that p53 represses the expression of the tricarboxylic-acid-cycle-associated malic enzymes ME1 and ME2 in human and mouse cells Both malic enzymes are important for NADPH production, lipogenesis and glutamine metabolism, but ME2 has a more profound effect Through the inhibition of malic enzymes, p53 regulates cell metabolism and proliferation Downregulation of ME1 and ME2 reciprocally activates p53 through distinct MDM2- and AMP-activated protein kinase-mediated mechanisms in a feed-forward manner, bolstering this pathway and enhancing p53 activation Downregulation of ME1 and ME2 also modulates the outcome of p53 activation, leading to strong induction of senescence, but not apoptosis, whereas enforced expression of either malic enzyme suppresses senescence Our findings define physiological functions of malic enzymes, demonstrate a positive-feedback mechanism that sustains p53 activation, and reveal a connection between metabolism and senescence mediated by p53

396 citations

Journal ArticleDOI
TL;DR: The biochemistry of lipid accumulation has been investigated in yeasts and filamentous fungi and can now be described in some detail and it is proposed that ME is physically attached to FAS as part of the lipogenic metabolon.
Abstract: A small number of eukaryotic micro-organisms, the oleaginous species, can accumulate triacylglycerols as cellular storage lipids, sometimes up to 70% of the biomass. Some of these lipids, particularly those containing high proportions of polyunsaturated fatty acids of nutritional and dietary importance, are now in commercial production; these are known as single-cell oils. The biochemistry of lipid accumulation has been investigated in yeasts and filamentous fungi and can now be described in some detail: lipid accumulation is triggered by cells exhausting nitrogen from the culture medium, but glucose continues to be assimilated. Activity of isocitrate dehydrogenase within the mitochondrion, however, now slows or even stops due to the diminution of AMP within the cells. This leads to the accumulation of citrate, which is transported into the cytosol and cleaved to acetyl-CoA by ATP:citrate lyase, an enzyme that does not occur in non-oleaginous species. This enzyme is therefore essential for lipid accumulation. The presence of this enzyme does not, however, explain why different species of oleaginous micro-organisms have different capacities for lipid accumulation. The extent of lipid accumulation is considered to be controlled by the activity of malic enzyme (ME), which acts as the sole source of NADPH for fatty acid synthase (FAS). If ME is inhibited, or genetically disabled, then lipid accumulation is very low. There is no general pool of NADPH which can otherwise be used by FAS. The stability of ME is therefore crucial and it is proposed that ME is physically attached to FAS as part of the lipogenic metabolon. ME activity correlates closely with lipid accumulation in two filamentous fungi, Mucor circinelloides and Mortierella alpina. When ME ceases to be active, lipid accumulation also stops. No other enzyme activity shows such a correlation.

380 citations

Journal ArticleDOI
TL;DR: Analysis of oxidative pathways of glutamine and glutamate showed that extramitochondrial malate is oxidized almost quantitatively to pyruvate + CO2 by NAD(P)+-linked malic enzyme, present in the mitochondria of all tumors tested, but absent in heart, liver, and kidney mitochondria.

374 citations

Journal ArticleDOI
TL;DR: Proteomic and metabolic analysis of Arabidopsis thaliana plants subjected to a combination of drought and heat stress suggests that cytosolic APX1 plays a key role in the acclimation of plants to aCombined drought andHeat stress.

370 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202326
202222
202124
202017
201916
201817