Redox and detox: Malate shuttle metabolism keeps exhausted T cells fit

Alok Kumar; Greg M Delgoffe

doi:10.1016/j.cmet.2023.11.005

Redox and detox: Malate shuttle metabolism keeps exhausted T cells fit

Cell Metab. 2023 Dec 5;35(12):2101-2103. doi: 10.1016/j.cmet.2023.11.005.

Authors

Alok Kumar¹, Greg M Delgoffe²

Affiliations

¹ Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
² Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: gdelgoffe@pitt.edu.

PMID: 38056428
DOI: 10.1016/j.cmet.2023.11.005

Abstract

The malate shuttle is known to maintain the balance of NAD⁺/NADH between the cytosol and mitochondria. However, in T_ex cells, it primarily detoxifies ammonia (via GOT1-mediated production of 2-KG in an atypical reaction) and provides longevity to chronic-infection-induced T_ex cells against ammonia-induced cell death.

MeSH terms

Ammonia* / metabolism
Aspartic Acid / metabolism
Cytosol / metabolism
Malate Dehydrogenase / metabolism
Malates* / metabolism
Mitochondria / metabolism
NAD / metabolism
Oxidation-Reduction
T-Lymphocytes / metabolism

Substances

Malates
Ammonia
NAD
Aspartic Acid
Malate Dehydrogenase