Table 1.

Term	Definition in the context of this review
Aerobic glycolysis	The metabolic pathway which utilizes glucose to generate ATP in the presence of oxygen. End products of this process are pyruvate which can be imported into mitochondria for use in the TCA cycle or lactate which is expelled from the cell as waste.
Anabolism	The enzymatic synthesis of molecules from smaller components.
Anaplerosis	The replenishment of metabolic intermediates into the TCA cycle as substrates for biosynthesis and the generation of ATP.
Bioenergetics	The study of energy production by cells. Often associated with use of the Seahorse analyzer to assess glycolysis and oxidative phosphorylation rates in real time.
Catabolism	The enzymatic degradation of molecules into smaller products.
Cataplerosis	The removal of TCA cycle intermediates for use in biosynthesis or to prevent build up within mitochondria.
Electron transport chain	A set of complexes of the inner mitochondrial membrane that shuttle electrons from NADH and FADH2 to oxygen. The redox reactions of the chain produce an electrochemical gradient of protons across the membrane which drives synthesis of ATP by oxidative phosphorylation.
Hypoxia	Oxygen deficiency in tissues, such that oxygen tension is below that of healthy physiological conditions. Normal oxygen levels differ between tissues and therefore the level at which a tissue is considered to be hypoxic is variable. The RA joint has an oxygen tension of 8% in health and <3% in RA.
Imaging mass spectrometry	A mass spectrometry based technique which allows the spatial distribution of the metabolome to be visualized in a tissue section. This offers insights into where pathogenic metabolic changes are taking place in tissues and is yet to be applied to the synovium.
Immunometabolism	The research field which investigates metabolism in the context of immunity and inflammation. As stromal cells are crucial to both induction and resolution of these processes, we consider the study of their metabolic processes to be embedded in this field.
Metabolic coupling	The transfer of metabolites between cells in a manner which benefits the biosynthetic and bioenergetic requirements of the recipient cell.
Metabolic flux analysis	Also known as ‘stable isotope metabolic tracer analysis’, this is a 13C isotope tracing methodology involving incubation of cells with a stable isotope, quantitation of metabolite labeling using mass spectrometry or NMR spectroscopy, and computational fitting of the data to a model allowing estimates of pathway-specific flux.
Metabolic memory	Imprinting of a metabolic phenotype on a cell by cues within its microenvironment, such that the phenotype is maintained after the cues are removed or the cells is removed from the tissue.
Metabolome	All substrates, intermediates and products of metabolism associated with a given system or compartment. These may be intracellular or extracellular.
Metabolomics	Used synonymously with the term ‘metabolic profiling’, this is the identification and measurement of all or a targeted set of metabolites within a body fluid, cell population or tissue conducted by NMR spectroscopy or mass spectrometry.
Mitochondrial biogenesis	The generation of greater mitochondrial mass to increase the capacity for mitochondrial function and ATP production within a cell; this process is important to health but is uninvestigated in RA.
Mitochondrial dynamics	The balance and transition between mitochondrial fusion and fission, movement and degradation; processes which are important to health but in uninvestigated in RA.
Mitochondrial fission	The division of mitochondrial networks into individual, punctate organelles, principally controlled by outer membrane proteins DRP1 and FIS1.
Mitochondrial fusion	The formation of tubular mitochondrial networks through MFN1, MFN2 and OPA1 mediated joining of individual organelle membranes. This process is associated with increased ATP production and protection of mitochondrial DNA from reactive oxygen species.
Mitophagy	‘Mitochondrial-selective autophagy’. The selective degradation of defective mitochondria without the release of inflammatory mitochondria- associated DAMPS.
Oxidative phosphorylation	Generation of ATP by the mitochondrial ATP synthase and driven by the electrochemical gradient of protons generated by the electron transport chain.
Pentose phosphate pathway	The pathway which oxidizes glucose to generate NADPH for the maintenance of the cellular redox balance and 5 carbon sugars utilized in anabolic processes such as nucleic acid synthesis.
Positron emission tomography	Use of a radioactive tracer isotope incorporated into a metabolic substrate to visualize metabolizing cells in a whole organism. Commonly, labelled glucose is used to identify tumors but is also useful in highlighting sites of inflammation such as the RA joint.
Reverse Warburg effect –	The production of high energy metabolic intermediates by one cell to anaplerotically feed ATP production by a neighboring cell. Currently characterized only in epithelial tumors where cancer-associated fibroblast feed lactate and other metabolites to tumor cells through channels such as the monocarboxylate transporters.
TCA cycle	The tricarboxylic acid cycle is a series of chemical reactions which take place in the mitochondrial matrix generating ATP by substrate level phosphorylation and NADH and FADH2 by oxidation of fuel molecules. The NADH and FADH2 are further oxidized by the electron transport chain.
Warburg effect	Pathological increase in glycolysis associated with reduced oxidative phosphorylation despite the presence of oxygen. This describes a cellular bioenergetic phenotype classically associated with tumor cells but now also associated with activated immune cells.