Table 2. A survey of mitochondrial TCA cycle enzymes, comparing the reported structure and predicted stability in solution at physiological conditions. Structure and general protein information has been obtained from the UniProt (Wasmuth and Lima, 2017) database. Theoretical pi and stability predictions have been computed using the ProtParam server (Gasteiger et al., 2005). FAHD proteins are predicted to be unstable (marked in red), however, FAHD1 is understood to form a soluble and catalytic active homodimer (Pircher et al., 2011, 2015; Weiss et al., 2018a; Manjasetty et al., 2004), whereas all other unstable proteins are part of greater protein complexes (Wasmuth and Lima, 2017) (marked in green). Protein interaction of FAHD1 is likely (Huttlin et al., 2015) (see Table 3). The protein structure of FAHD2a and FAHD2b is yet unreported.

Enzyme	Name	UniProt-lD	UniProt- Spec	Theoretical pi	Instability index	Stability	Part of a complex	Structure
CS	Citrate synthase	075390	CISYJHUMAN	8.45	22.40	stable	no	homodimer
ACO	Aconitate hydratase	Q99798	ACON_HUMAN	7.36	34.70	stable	no	monomer
IDH2	Isocitrate dehydrogenase [NADP]	P48735	IDHPJHUMAN	8.88	29.77	stable	no	homodimer
	Isocitrate dehydrogenase [NAD] subunit alpha	P50213	IDH3AJHUMAN	6.46	41.24	unstable	yes (IDH3)	complex
IDH3	Isocitrate dehydrogenase [NAD] subunit beta	043837	DH3BJHUMAN	8.64	36.88	stable	yes (IDH3)	complex
	Isocitrate dehydrogenase [NAD] subunit gamma	P51553	IDH3GJHUMAN	8.75	45.59	unstable	yes (IDH3)	complex
	2-oxoglutarate dehydrogenase	Q02218	ODOIJHUMAN	6.39	45.17	unstable	yes (OGDC)	complex
OGDC	Dihydrolipoyllysine-residue succinyltransferase	P36957	0D02JHUMAN	9.10	50.53	unstable	yes (OGDC)	complex
	Dihydrolipoyl dehydrogenase	P09622	DLDH_HUMAN	7.95	28.07	stable	yes (OGDC)	complex
	Succinate--CoA ligase [ADP/GDP-forming] subunit alpha	P53597	SUCAJHUMAN	9.01	41.30	unstable	yes (SUCA/SUCG)	complex
SUC(A/G)	Succinate--CoA ligase [GDP-forming] subunit beta	Q96I99	SUCB2HUMAN	6.15	32.54	stable	yes (SUCG)	complex
	Succinate--CoA ligase [ADP-forming] subunit beta	Q9P2R7	SUCB1JHUMAN	7.05	41.13	unstable	yes (SUCA)	complex
	Succinate dehydrogenase [ubiquinone] flavoprotein subunit	P31040	SDHAJHUMAN	7.06	37.04	stable	yes (SDH)	complex
SDH	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit	P21912	SDHBJHUMAN	9.03	60.13	unstable	yes (SDH)	complex
	Succinate dehydrogenase cytochrome b560 subunit	Q99643	C560JHUMAN	9.74	47.79	unstable	yes (SDH)	complex
	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit	014521	DHSD_HUMAN	8.92	33.20	stable	yes (SDH)	complex
FH	Fumarate hydratase	P07954	FUMH_HUMAN	8.85	28.59	stable	no	homotetramer
MDH2	Malate dehydrogenase	P40926	MDHM_HUMAN	8.92	31.92	stable	no	homodimer
FAHD1	Fumarylacetoacetate hydrolase domain containing protein 1	Q6P587	FAHD1_HUMAN	6.96	42.36	unstable	likely	homodimer
FAHD2a	Fumarylacetoacetate hydrolase domain containing protein 2a	Q96GK7	FAH2A_HUMAN	8.48	41.26	unstable	unknown	unknown
FAHD2b	Fumarylacetoacetate hydrolase domain containing protein 2b	Q6P2I3	FAH2B_HUMAN	7.64	40.43	unstable	unknown	unknown