Krebs and an alternative TCA cycle!

Mary T Doan¹, Michael A Teitell^{2

3}

Affiliations

¹ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
² Department of Pathology and Laboratory Medicine, Department of Pediatrics and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. mteitell@mednet.ucla.edu.
³ Molecular Biology Institute, Department of Bioengineering, California NanoSystems Institute, and Broad Center for Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, CA, USA. mteitell@mednet.ucla.edu.

PMID: 35459937
PMCID: PMC9160273
DOI: 10.1038/s41422-022-00664-4

Comment

Krebs and an alternative TCA cycle!

Mary T Doan et al. Cell Res. 2022 Jun.

. 2022 Jun;32(6):509-510.

doi: 10.1038/s41422-022-00664-4.

Authors

Mary T Doan¹, Michael A Teitell^{2

3}

Affiliations

¹ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
² Department of Pathology and Laboratory Medicine, Department of Pediatrics and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. mteitell@mednet.ucla.edu.
³ Molecular Biology Institute, Department of Bioengineering, California NanoSystems Institute, and Broad Center for Regenerative Medicine and Stem Cell Research, University of California at Los Angeles, Los Angeles, CA, USA. mteitell@mednet.ucla.edu.

PMID: 35459937
PMCID: PMC9160273
DOI: 10.1038/s41422-022-00664-4

No abstract available

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Figures

**Fig. 1. A non-canonical TCA cycle.**
Arnold, Jackson and colleagues propose an alternative TCA cycle wherein citrate is exported out of the mitochondria (mito) to the cytosol (cyto) by citrate/malate antiporter SLC25A1 and then cleaved by ACL into (1) cytosolic acetyl-CoA for biosynthetic and acetylation reactions, and (2) oxaloacetate to regenerate NAD⁺ and produce malate, which is then imported into mitochondria to complete one turn of the TCA cycle without the loss of CO₂. Cytosolic citrate could also contribute to nuclear (nuc) citrate concentrations, wherein ACL also converts citrate into acetyl-CoA to power acetylation reactions. Created with BioRender.com.

See this image and copyright information in PMC

Comment on

A non-canonical tricarboxylic acid cycle underlies cellular identity.
Arnold PK, Jackson BT, Paras KI, Brunner JS, Hart ML, Newsom OJ, Alibeckoff SP, Endress J, Drill E, Sullivan LB, Finley LWS. Arnold PK, et al. Nature. 2022 Mar;603(7901):477-481. doi: 10.1038/s41586-022-04475-w. Epub 2022 Mar 9. Nature. 2022. PMID: 35264789 Free PMC article.

References

1. Metallo CM, Vander Heiden MG. Mol. Cell. 2013;49:388–398. doi: 10.1016/j.molcel.2013.01.018. - DOI - PMC - PubMed
1. Krebs HA, Johnson WA. Biochem. J. 1937;31:645–660. doi: 10.1042/bj0310645. - DOI - PMC - PubMed
1. Kim J, DeBerardinis RJ. Cell Metab. 2019;30:434–446. doi: 10.1016/j.cmet.2019.08.013. - DOI - PMC - PubMed
1. Arnold PK, et al. Nature. 2022;603:477–481. doi: 10.1038/s41586-022-04475-w. - DOI - PMC - PubMed
1. Krebs HA, Eggleston LV. Biochem. J. 1940;34:442–459. doi: 10.1042/bj0340442. - DOI - PMC - PubMed

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Krebs and an alternative TCA cycle!

Affiliations

Krebs and an alternative TCA cycle!

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