REAGENT or RESOURCE	SOURCE	IDENTIFIER
Bacterial and virus strains
E. coli OP50	Caenorhabditis Genetics Center (CGC)	N/A
E. coli HT115(DE3) with alh-6 and empty RNAi clones	N/A	N/A
Chemicals, peptides, and recombinant proteins
Pronase	Sigma	Cat#P5147
Monensin	Sigma	Cat#M5273
Mitotracker	Thermofisher	Cat#M7512
JC-1	Invitrogen	Cat#T3168
NpFR1	Yeow et al.49	N/A
NpFR2	Kaur et al.48	N/A
N-acetyl Cysteine	Sigma	Cat#A7250
Critical commercial assays
Dneasy blood and tissue kit	QIAGEN	Cat#69504
TruSeq Nano DNA Sample Preparation Kit	Illumina	Cat#20015965
Experimental models: Organisms/strains
C. elegans: N2: Wild-type, Bristol isolate	CGC	N/A
C. elegans: SX461: mjIs31[ppie-1::gfp::h2b] II	(Ashe et al., 2012)	N/A
C. elegans: AKA361: set-32(ok1457) I; sdha-2(smb65) I; mjIs31[ppie-1::gfp::h2b] II	Woodhouse et al.20	N/A
C. elegans: FX01420 (used in Figure 1B): sdha-2(tm1420) I	NBRP	N/A
C. elegans: FX31204: col-60(tm10278) I	NBRP	N/A
C. elegans: RB1480: nra-2(ok1731) I	International C. elegans Gene Knockout Consortium	N/A
C. elegans: EU1135: tba-1(or346) I	(Phillips et al., 2004)	N/A
C. elegans: EU1161: tba-1(or594) I	(O’Rourke et al., 2011)	N/A
C. elegans: RB1185: tba-1(ok1135) I	International C. elegans Gene Knockout Consortium	N/A
C. elegans: FX31000: mgl-2(tm8806) I	NBRP	N/A
C. elegans: FX00355: mgl-2(tm355) I	NBRP	N/A
C. elegans: CB698: vab-10(e698) I	(Hodgkin, 1983)	N/A
C. elegans: VC117: vab-10(gk45) I	International C. elegans Gene Knockout Consortium	N/A
C. elegans: AKA156: F30A10.15(smb55) I; mjIs31[ppie-1::gfp::h2b] II	This paper. Outcrossed 2x following generation by CRISPR-Cas9	N/A
C. elegans: AKA157: marc-3(smb53) I; mjIs31[ppie-1::gfp::h2b] II	This paper. Outcrossed 2x following generation by CRISPR-Cas9	N/A
C. elegans: AKA136 (used in every instance except Figure 1B): sdha-2(tm1420) I; mjIs31[ppie-1::gfp::h2b] II	This paper. Outcrossed 7x from FX01420	N/A
C. elegans: AKA145 (referred to as AKA36[sdha-2(+)] in this paper): set-32(ok1457) I; mjIs31[ppie-1::gfp::h2b] II	This paper. Derived from AKA36: sdha-2(smb65) repaired back to wild-type sequence by CRISPR-Cas9. Outcrossed 4x	N/A
C. elegans: AKA199: sdha-2(smb65) I; mjIs31[ppie-1::gfp::h2b] II	This paper. Outcrossed 6x following generation by CRISPR-Cas9	N/A
C. elegans: AKA59: mjIs31[ppie-1::gfp::h2b] II; rhIs4[glr-1::gfp] III; him-8(e1489) IV	Woodhouse et al.20	N/A
C. elegans: AKA60: set-32(ok1457) I; sdha-2(smb65) I; mjIs31[ppie-1::gfp::h2b] II, rhIs4[glr-1::gfp] III; him-8(e1489) IV	Woodhouse et al.20)	N/A
C. elegans: AKA205: sdha-2(tm1420) I; mjIs31[ppie-1::gfp::h2b] II, rhIs4[glr-1::gfp] III; him-8(e1489) IV	This paper	N/A
C. elegans: AKA207: set-32(ok1457) I; mjIs31[ppie-1::gfp::h2b] II, rhIs4[glr-1::gfp] III; him-8(e1489) IV	This paper	N/A
C. elegans: AKA25: mjIs31[ppie-1::gfp::h2b] II; him-8(e1489) IV	This paper. Outcrossed 1x from CB1489	N/A
C. elegans: AKA55: set-32(ok1457) I; sdha-2(smb65) I; mjIs31[ppie-1::gfp::h2b] II; him-8(e1489) IV	This paper	N/A
C. elegans: AKA131: sdha-2(tm1420) I; him-8(e1489) IV	This paper	N/A
C. elegans: VC1434: +/szT1 [lon-2(e678)] I; sdha-1(ok1908)/szT1 X, VC294 sdhb-1(gk165)/mIn1 [mIs14 dpy-10(e128)] II	International C. elegans Gene Knockout Consortium	N/A
C. elegans: VC848: sdhc-1(ok909) III/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III)2	International C. elegans Gene Knockout Consortium	N/A
C. elegans: TK22: sdhc-1(kn1) III2	Ishii et al.35	N/A
C. elegans: VC1497: fum-1(ok1998) III/hT2 [bli-4(e937) let-?(q782) qIs48] (I;III)	International C. elegans Gene Knockout Consortium	N/A
C. elegans: RB766: icl-1(ok531) V	International C. elegans Gene Knockout Consortium	N/A
C. elegans: ZB5206: sdha-2(tm1420) I; icl-1(ok531) V	This paper, outcrossed 4x	N/A
C. elegans: CB1489: him-8(e1489) IV	(Hodgkin et al., 1979)	N/A
C. elegans: SJ4100: zcIs13[phsp-6::GFP] V	Yoneda et al.33	N/A
C. elegans: AKA161: sdha-2(tm1420) I; zcIs13[phsp-6::GFP] V	This paper	N/A
C. elegans: SJ4058: zcIs9 [phsp-60::GFP + lin-15(+)] V	Yoneda et al.33	N/A
C. elegans: AKA164: sdha-2(tm1420) I; zcIs9 [phsp-60::GFP + lin-15(+)] V	This paper	N/A
C. elegans: CL2166: dvIs19 [(pAF15)pgst-4::GFP::NLS] III	Link and Johnson,47	N/A
C. elegans: AKA155: sdha-2(tm1420) I; dvIs19 [(pAF15)pgst-4::GFP::NLS] III	This paper	N/A
Oligonucleotides
Sequences of CRISPR guides and repair templates used in this study	This study	Table S2
Alt-R® CRISPR-Cas9 tracrRNA	IDT	Cat#1072532
Recombinant DNA
pHO4d-Cas9	Fu et al.72	Addgene plasmid #67881
Software and algorithms
Custom Alt-R® CRISPR-Cas9 guide RNA design tool	IDT	https://sg.idtdna.com/site/order/designtool/index/CRISPR_CUSTOM
I-TASSER	Roy et al.21	https://zhanglab.ccmb.med.umich.edu/I-TASSER/
PyMOL	PyMOL by Schrödinger	https://pymol.org/
Fiji (ImageJ)	ImageJ	https://imagej.net/software/fiji/
GraphPad Prism 9	GraphPad	https://www.graphpad.com/ RRID: SCR_002798
CLC Genomics	QIAGEN	https://digitalinsights.qiagen.com/
WormBase	WormBase	https://wormbase.org/
R version 4.1.0	R Project	https://www.r-project.org/
RStudio version 1.4.1717	RStudio	https://www.rstudio.com/
Cutadapt version 1.8.3	Martin,73	https://doi.org/10.14806/ej.17.1.200
STAR aligner	Dobin et al.74	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530905/
DESeq2	R Package (Love et al.75)	https://bioconductor.org/packages/release/bioc/html/DESeq2.html
GSEA	Broad Institute, Subramanian et al.76	https://www.gsea-msigdb.org/gsea/index.jsp
ggplot2	R library	https://ggplot2.tidyverse.org/
ComplexHeatmap	R Package Gu et al.77	https://bioconductor.org/packages/release/bioc/html/ComplexHeatmap.html
ShinyGO	Ge et al.78	http://bioinformatics.sdstate.edu/go/