Arnold 2023 J Biol Chem

Arnold PK, Finley LWS (2022) Regulation and function of the mammalian tricarboxylic acid cycle. J Biol Chem 299:102838. doi: 10.1016/j.jbc.2022.102838

» PMID: 36581208 Open Access

Arnold PK, Finley LWS (2022) J Biol Chem

Abstract: The tricarboxylic acid (TCA) cycle, otherwise known as the Krebs cycle, is a central metabolic pathway that performs the essential function of oxidizing nutrients to support cellular bioenergetics. More recently, it has become evident that TCA cycle behavior is dynamic, and products of the TCA cycle can be co-opted in cancer and other pathologic states. In this review, we revisit the TCA cycle, including its potential origins and the history of its discovery. We provide a detailed accounting of the requirements for sustained TCA cycle function and the critical regulatory nodes that can stimulate or constrain TCA cycle activity. We also discuss recent advances in our understanding of the flexibility of TCA cycle wiring and the increasingly appreciated heterogeneity in TCA cycle activity exhibited by mammalian cells. Deeper insight into how the TCA cycle can be differentially regulated and, consequently, configured in different contexts will shed light on how this pathway is primed to meet the requirements of distinct mammalian cell states.

• Bioblast editor: Gnaiger E

Correction: FADH₂ and S-pathway

• Complex II ambiguities

A commonly found error on FADH₂ in the S-pathway requires correction. For clarification, see page 48 in Gnaiger (2020)

• Quote (p 48): "The substrate of CII is succinate, which is oxidized forming fumarate while reducing flavin adenine dinucleotide FAD to FADH₂, with further electron transfer to the quinone pool. Whereas reduced NADH is a substrate of Complex I linked to dehydrogenases of the TCA cycle and mt-matrix upstream of CI, reduced FADH₂ is a product of Complex II with downstream electron flow from CII to Q."

Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002