KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit polyclonal anti-MT-CO1	Novus biologicals	Cat# NBP2-29949
Rabbit polyclonal anti-MT-ND6	Novus biologicals	Cat# NBP1-70650; RRID: AB_11006834
Mouse monoclonal anti-MT-ATP6 (clone 1G7-1G2)	Sigma-Aldrich	Cat#: MABS1995
Rabbit monoclonal anti-NDUFB8 (clone JG61-36)	Novus biologicals	Cat# NBP2-75586
Rabbit monoclonal anti-SDHA (clone D6J9M)	Cell Signaling Technology	Cat# 11998; RRID: AB_2750900
Mouse monoclonal anti-ATP5A (clone 15H4)	Abcam	Cat# ab14748; RRID: AB_301447
Rabbit monoclonal anti-GLUD1(clone EPR11369(B))	Abcam	Cat# ab166618; RRID: AB_2815030
Rabbit monoclonal anti-ME2 (clone EPR7218)	Abcam	Cat#:ab126616; RRID: AB_11131748
Mouse polyclonal anti-POLRMT	Abcam	Cat#:ab167368
Mouse monoclonal anti-NRF2	Abcam	Cat#: ab89443; RRID: AB_2041334
Rabbit polyclonal anti-PGC1α	Abcam	Cat#: ab54481; RRID: AB_881987
Mouse monoclonal anti-beta-Actin (clone 8H10D10)	Cell Signaling Technology	Cat#:3700; RRID: AB_2242334
Rabbit polyclonal anti-GAPDH	Proteintech	Cat#: 10494-1-AP; RRID: AB_2263076
Mouse monoclonal anti-Histone H3 (clone 96C10)	Cell Signaling Technology	Cat#:3638; RRID: AB_1642229
Mouse monoclonal anti-Flag (clone M2)	Sigma-Aldrich	Cat#:F1804; RRID: AB_262044
Rabbit polyclonal anti-ME1	Abcam	Cat#:ab97445; RRID: AB_10679994
Rabbit monoclonal anti-ME2 (clone EP7217)	Abcam	Cat#: ab139686
Rabbit monoclonal anti-ME3 (clone EPR10378)	Abcam	Cat#:ab172972
Rabbit polyclonal anti-ACO2	Proteintech	Cat#: 11134-1-AP
Rabbit polyclonal anti-2SC antibody	Discovery Antibodies	Cat#: crb2005017
Rabbit polyclonal anti-DUT	Proteintech	Cat#: 13740-1-AP
Rabbit polyclonal anti-GOT2	Proteintech	Cat#: 14800-1-AP
Mouse monoclonal anti-GFP (clone 9F9.F9)	Abcam	Cat#:ab1218; RRID: AB_298911
Mouse monoclonal anti-HA (clone F-7)	Santa Cruz	Cat#:sc-7392; RRID: AB_627809
Rabbit polyclonal anti-MRPL45	Sigma-Aldrich	Cat# HPA023373; RRID: AB_1854114
Rabbit monoclonal anti-MRRF [clone EPR14140(B)]	Abcam	Cat#: ab181223
Rabbit polyclonal anti-MRPL12	Abcam	Cat#: ab154961
Rabbit monoclonal anti-MRPS35 [clone EPR11731(2)]	Abcam	Cat#: ab182160
Rabbit polyclonal anti-MT-ND5	Proteintech	Cat#: 55410-1-AP
Rabbit polyclonal anti-MT-CYB	Proteintech	Cat#: 55090-1-AP
Rabbit polyclonal anti-MT-CO2	Proteintech	Cat#: 55070-1-AP
Mouse monoclonal anti-His (clone 27E8)	Cell Signaling Technology	Cat# 2366; RRID: AB_2115719
Rabbit monoclonal anti-TOM20 (clone 29)	BD Biosciences	Cat#612278; RRID: AB_399595
Rabbit polyclonal anti-me-ME2(R67)	This paper	N/A
Rabbit polyclonal anti-PRMT1	Abcam	Cat#:2449; RRID: AB_2237696
Rabbit monoclonal anti-Mono-Methyl Arginine (clone Me-R4-100)	Cell Signaling Technology	Cat#:8015; RRID: AB_10891776
Mouse monoclonal anti-CARM1	Arigo Biolaboratories	Cat#: ARG53996
Bacterial strains
Escherichia coli BL21	Invitrogen	C600003
Chemicals, peptides, and recombinant proteins
MitoTracke Green FM	Invitrogen	M7514
Dimethyl fumarate	Sigma-Aldrich	242926; CAS: 624-49-7
Diethyl fumarate	Sigma-Aldrich	D95654; CAS: 623-91-6
Sodium fumarate dibasic	Sigma-Aldrich	F1506; CAS: 17013-01-3
Monomethyl fumarate	Sigma-Aldrich	651419; CAS: 2756-87-8
Monoethyl fumarate	Sigma-Aldrich	128422; CAS: 2459-05-4
Dimethyl malate	Sigma-Aldrich	374318; CAS: 617-55-0
Diethyl oxalacetate	Sigma-Aldrich	171263; CAS: 40876-98-0
MEM Non-essential Amino Acid Solution	Sigma-Aldrich	M7145
MEM Amino Acids solution	Sigma-Aldrich	M5550
[U-13C]-fumarate	Cambridge Isotope Laboratories	CLM-1529; CAS: 201595-62-2
Maleimide-PEG2-Biotin	Thermo Scientific	A39261
Glutaraldehyde	Sigma-Aldrich	340855; CAS: 111-30-8
TAS114	MedChemExpress	HY-124062; CAS: 1198221-21-4
Succinate	Sigma-Aldrich	S9637; CAS: 6106-21-4
Malate	Sigma-Aldrich	M1000; CAS: 97-67-6
AMI-1 sodium salt hydrate	Sigma-Aldrich	A9232
AMI-5	EMD Millipore	539211; CAS: 17372-87-1
TC-E 5003	Tocris	5099
S-adenosylmethionine	Sigma-Aldrich	A9384; CAS: 979-92-0
Unmodified R67 peptide	This paper	N/A
Monomethylated R67 peptide	This paper	N/A
Recombinant Human ME2 protein	Abcam	ab201360
SYPRO orange protein gel stain	Invitrogen	S6650
Critical commercial assays
Glucose (GO) Assay Kit	Sigma-Aldrich	GAGO20
Glutamine and Glutamate Determination Kit	Sigma-Aldrich	GLN1
Mitochondria Isolation Kit	Sigma-Aldrich	MITOISO2
Glutamine Detection Assay Kit (Colorimetric)	Abcam	ab197011
Fumarate Assay Kit	Sigma-Aldrich	MAK060
NAD/NADH Quantitation Kit	Sigma-Aldrich	MAK037
Luminescent ATP Detection Assay Kit	Abcam	ab113849
Seahorse XF Cell Mito Stress Test Kit	Agilent	103015
MagniSort Mouse Hematopoietic Lineage Depletion Kit	Invitrogen	8804-6829-74
Deposited data
Proteomic data	This paper	MassIVE:MSV000086778
Experimental models: Cell lines
Human Cord Blood CD34+ Cells	STEMCELL Technologies	70008
Human:HL60	ATCC	CCL-240
Human:THP1	ATCC	TIB-202
Human:NOMO1	JCRB Cell Bank	IFO50474
Human:KG1	ATCC	CCL-246.1
Human:NB4	DSMZ	ACC-207
Human:MONOMAC6	DSMZ	ACC-124
Human:MOLM14	DSMZ	ACC-777
Human:MV411	ATCC	CRL-9591
Human:HEK293	ATCC	CRL-1573
Human:A172	ATCC	CRL-1620
Human:LN18	ATCC	CRL-2610
Human:U87MG	ATCC	HTB-14
Human:U251MG	Sigma-Aldrich	09063001
Human:U118MG	ATCC	HTB-15
Human:BT549	ATCC	HTB-122
Human:HCC1937	ATCC	CRL-2336
Human: HCC38	ATCC	CRL-2314
Human: HS578T	ATCC	HTB-126
Human: MDAMB231	ATCC	HTB-26
Human: MDAMB468	ATCC	HTB-132
Human: HepG2	ATCC	HB-8065
Human: SKHEP1	ATCC	HTB-52
Human: SNU423	ATCC	CRL-2238
Human: SNU387	ATCC	CRL-2237
Human: A375	ATCC	CRL-1619
Human: SKMEL5	ATCC	HTB-70
Human: SKMEL28	ATCC	HTB-72
Human: MIAPaCa2	ATCC	CRM-CRL-1420
Human: KP2	JCRB Cell Bank	JCRB0181
Human: AsPC1	ATCC	CRL-1682
Human: SW1990	ATCC	CRL-2172
Human: BxPC3	ATCC	CRL-1687
Human: U2OS	ATCC	HTB-96
Human: HeLa	ATCC	CCL-2
Human: DU145	ATCC	HTB-81
Human: HCT116	ATCC	CCL-247
Human: HT1080	ATCC	CCL-121
Experimental models: Organisms/strains
Mouse: C57BL/6J	The Jackson Laboratory	JAX: 000664
Mouse: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ	The Jackson Laboratory	JAX: 005557
Recombinant DNA
Human ME2 Mission shRNA-#1	Sigma-Aldrich	TRCN0000064742
Human ME2 Mission shRNA-#2	Sigma-Aldrich	TRCN0000294007
Human ADSL Mission shRNA-#1	Sigma-Aldrich	TRCN0000078272
Human ADSL Mission shRNA-#2	Sigma-Aldrich	TRCN0000078271
Human ASL Mission shRNA-#1	Sigma-Aldrich	TRCN0000078310
Human ASL Mission shRNA-#2	Sigma-Aldrich	TRCN0000078312
Human FAH Mission shRNA-#1	Sigma-Aldrich	TRCN0000296459
Human FAH Mission shRNA-#2	Sigma-Aldrich	TRCN0000050674
Human SDHA Mission shRNA-#1	Sigma-Aldrich	TRCN0000028118
Human SDHA Mission shRNA-#2	Sigma-Aldrich	TRCN0000028093
Human PRMT1 Mission shRNA-#1	Sigma-Aldrich	TRCN0000310243
Human PRMT1 Mission shRNA-#2	Sigma-Aldrich	TRCN0000035931
Mouse Me2 Mission shRNA-#1	Sigma-Aldrich	TRCN0000332396
Mouse Me2 Mission shRNA-#2	Sigma-Aldrich	TRCN0000332397
pcDNA3.1	Invitrogen	V80020
pcDNA3.1-ME2-Flag	This study	N/A
pcDNA3.1-ME2-HA	This study	N/A
lentiCRISPR v2	Addgene	Cat#52961
pLV-EF1a-IRES-Hygro	Addgene	Cat#85134
pLV-EF1a-IRES-Hygro-ME2-Flag	This study	N/A
pLV-EF1a-IRES-Hygro-NRF2-Flag	This study	N/A
pLV-EF1a-IRES-Hygro-SLC1A3-Flag	This study	N/A
pEGFP-N1-FLAG	Addgene	Cat#60360
pEGFP-N1-FLAG-ME2	This study	N/A
pEGFP-PRMT1-9	(Herrmann et al., 2009)	N/A
pcDNA3.1-MRPL45-HA	This study	N/A
pEGFPN1-MRPL45	This study	N/A
pQE1-MRPL45	This study	N/A
pSJ3-ME2-His	This study	N/A
Software and algorithms
FlowJo, version 10	FlowJo	N/A
PyMol2.1	https://pymol.org/2/	N/A
GraphPad Prism 8	https://www.graphpad.com/	N/A