ATP Synthesis-coupled and -uncoupled Acetate Production from Acetyl-CoA by Mitochondrial Acetate:Succinate CoA-transferase and Acetyl-CoA Thioesterase in Trypanosoma

Abstract

Background: Mitochondrial acetate production is essential for viability of the procyclic trypanosomes and probably many other protists. Results:We identified an acetyl-CoA thioesterase (ACH) contributing to acetate production from acetyl-CoA. Conclusion: Acetate production by ASCT, but not by ACH, is involved in ATP production. Significance: In trypanosomes and probably other protists, ASCT/SCoAS cycle-derived ATP production can substitute for oxidative phosphorylation.

Contribution of Pyruvate Phosphate Dikinase in the Maintenance of the Glycosomal ATP/ADP Balance in the Trypanosoma brucei Procyclic Form

“…1B). This is probably due to the limited capacity of acetate production, as previously proposed (50). The same analyses revealed that the ⌬ppdk/⌬pepck cell line behaves differently.…”

Functional Characterization of TbMCP5, a Conserved and Essential ADP/ATP Carrier Present in the Mitochondrion of the Human Pathogen Trypanosoma brucei

“…This result is in agreement with previously published data indicating that no or very low amounts of acetate are produced from proline, whereas the degradation of threonine is the main source of acetate production under glucose-depleted conditions (9,46). Acetate can be produced in the mitochondrion from threoninederived acetyl-CoA via acetate:succinate CoA-transferase (ASCT)-dependent (47,48) and by acetyl-CoA thioesterase (ACH)-dependent pathways (49). An important difference between these pathways is that ASCT, forming the ASCT/ SCoAS cycle in association with succinyl-CoA synthase (SCoAS), results in the production of ATP via substrate level phosphorylation, whereas the ACH pathway does not lead to ATP production (47)(48)(49).…”

“…Acetate can be produced in the mitochondrion from threoninederived acetyl-CoA via acetate:succinate CoA-transferase (ASCT)-dependent (47,48) and by acetyl-CoA thioesterase (ACH)-dependent pathways (49). An important difference between these pathways is that ASCT, forming the ASCT/ SCoAS cycle in association with succinyl-CoA synthase (SCoAS), results in the production of ATP via substrate level phosphorylation, whereas the ACH pathway does not lead to ATP production (47)(48)(49). Silencing of SCoAS expression by RNAi confirmed that acetate could be exclusively produced from threonine by ACH (49).…”

“…An important difference between these pathways is that ASCT, forming the ASCT/ SCoAS cycle in association with succinyl-CoA synthase (SCoAS), results in the production of ATP via substrate level phosphorylation, whereas the ACH pathway does not lead to ATP production (47)(48)(49). Silencing of SCoAS expression by RNAi confirmed that acetate could be exclusively produced from threonine by ACH (49). This pathway does not result in ATP production and is thus not dependent on a functional mitochondrial ADP/ATP carrier.…”

Alternative Acetate Production Pathways inChlamydomonas reinhardtiiduring Dark Anoxia and the Dominant Role of Chloroplasts in Fermentative Acetate Production

“…These include: (a) the spontaneous hydrolysis of acetate phosphate to acetate and P i (Koshland, 1952;Di Sabato and Jencks, 1961); (b) aldehyde dehydrogenase activity that oxidizes acetaldehyde (from pyruvate decarboxylation) to acetate (Kirch et al, 2004(Kirch et al, , 2005Brocker et al, 2013); (c) acetyl-CoA hydrolase, which hydrolyzes acetyl-CoA to acetate and CoA without the production of ATP (Tielens et al, 2010); (d) acetate formation by AMP-forming acetyl-CoA synthetase (Takasaki et al, 2004;Yoshii et al, 2009); and (e) ASCT and SCL activities (van Grinsven et al, 2008;Millerioux et al, 2012). ASCT transfers the CoA moiety of acetyl-CoA to succinate and SCL converts succinyl-CoA back to succinate.…”