A
acetyl CoA
malonyl CoA
saturated fatty acylCoAs
monounsaturated fatty acylCoAs
triglycerides
storage/export
CPT
mitochondrial
ß-oxidation
pod-2
fasn-1
fat-5, fat-6, fat-7
Perhexiline (PHX)
B
0
200
400
600
800
1000
1200
1400
Control EV:hsp-6 hsp-6:pod-2hsp-6:fasn-1
GFP Fluorescence (RFU)
**
* **
0
100
200
300
400
500
600
700
Control dve-1 hsf-1 clpp-1 atfs-1
GFP Fluorescence (RFU)
Control
PHX
**
C
EV: hsp-6 hsp-6:pod-2 hsp-6:fasn-1
hsp-16.2p::GFP
Double RNAi with hsp-6
Control (EV) dve-1 hsf-1 clpp-1 atfs-1 RNAi
hsp-16.2p::GFP
DMSO (Control)
PHX treatment
Control (EV) dve-1 hsf-1 clpp-1 atfs-1 RNAi
hsp-16.2p::GFP
hsp-16.2p::GFP
Figure 4. Reducing Fat Synthesis Blocks Cytosolic Response, and Inhibiting CPT Activity Induces Cytosolic Stress Response
(A) Diagram showingC. elegansgenes involved in the fat storage pathway.pod-2, acyl-CoA carboxylase;fasn-1, fatty acid synthase;fat-5,fat-6, andfat-7,
delta-9 fatty acid desaturase; CPT, carnitine palmitoyltransferase.
(B) Knocking down two enzymes involved in fat synthesis inhibited cytosolic response. (Continued fromFigure 1C; note that the image of control worms are from
Figure 1C.)hsp-16.2p::GFP reporter induction was measured by COPAS biosorter (bottom) (mean±SD of three biological repeats; *p%0.05, p%0.01).
(C) CPT inhibitor PHX-treated hsp-16.2p::GFP;CF512 reporter worms showed elevated levels of GFP that were inhibited byhsf-1and UPRmtcomponents. GFP
induction was measured by COPAS biosorter (right) (mean±SD of three biological repeats; p%0.01).
See alsoFigure S4.
Cell 166 , 1539–1552, September 8, 2016 1545