Figure 1. Genetic screen identifies additional proteins involved in the maintenance of mitochondrial homeostasis. A. The candidates identified in the screen are listed by functional groups. When available, the name of the human ortholog as stated on Alliancegenome.org is indicated. Protein localization is indicated and is based on experimental evidence in C. elegans or experimental evidence using the human ortholog. In case no experimental evidence was available, the localization was predicted with the PSORT II website (https://psort.hgc.jp/form2.html). Newly identified candidates are indicated in green whereas candidates identified in previous genetic screens are indicated in blue (Runkel et al. 2013, Bennett et al. 2014).Finally, candidates identified in a previous genetic screen for enhancers of
fzo-1(
tm1133lf)-induced UPRmt are indicated in yellow (Haeussler et al. 2021). B. DIC and fluorescence images of animals carrying the
hsp-6p::GFP (zcIs13) reporter and either homozygous for the C25H3.11 loss-of-function allele
ok2632 (C25H3.11
(ok2632)) or homozygous wildtype for C25H3.11 (mIn1/mIn1). The balancer mIn1 carries the
dpy-10(
e128) mutation and the pharyngeal
myo-2p::GFP transgene, which is visible in the mIn1/mIn1 Dumpy animal (indicated by an arrow in the right panel). Induction of the
hsp-6p::GFP reporter is visible in the intestine of C25H3.11
(ok2632) homozygous animals (indicated by an arrowhead in the right panel) but not in animals homozygous for the balancer mIn1. C. Wild-type (+/+) and C25H3.11
(ok2632) animals were analyzed by Western analysis using anti-tubulin (loading control) and anti-GFP antibodies. D. C25H3.11 VPS13D has been proposed to be a conduit that transfers lipids between ER and mitochondria and between ER and peroxisomes (Guillen-Samander et al. 2021). It localizes to the ER in a VPR-1 VAP-B dependent manner (Guillen-Samander et al. 2021). PRX-3 PEX3 and PRX-12 PEX12 are essential for peroxisome biogenesis and hence peroxisomal beta oxidation (Petriv et al. 2002). Inactivation of any of thesegenes induces the expression of the
hsp-6p::GFP reporter and hence triggers UPRmt, indicating that these proteins are required to maintain mitochondrial homeostasis.