Nature - USA (2020-09-24)

Article

b

d

-Log

p adj. 10

Major functional pathways in peroxisomes

Catalase

ROS

H 2 O 2

H 2 O+O 2

Acyl-CoA

DHAP

Ether-lipids

(e.g. plasmalogens)

AGPS

VLCFA-CoA

BCFA-CoA

Other acyl-CoA

a

-2 -1 0

sgNC

AGPS-sg1

AGPS-sg2

OVCAR-8

0.0

0.4

0.8

1.2

sgNC

FAR1-sg1

FAR1-sg2

OVCAR-8

c

Log 10 (M RSL3)

f

h

sgNC

AGPS-sg2

AGPS-sg1

786-O

-2 -1 0

0.0

0.4

0.8

1.2

Log 10 (M ML210)

Relative

viabilit

y

-3 -2 -1

sgNC

FAR1-sg1

FAR1-sg2

786-O:

Log 10 (M RSL3)

g

-2 -1 0

0.0

0.4

0.8

1.2

Log 10 (M ML210)

Relativ

ev

iabilit

y

AGPS

β-Actin

sgNC sg1 sg2

FAR1

β-Actin

sgNC sg1 sg2

786-O

786-O

i

sgNC

AGPS-sg2

FAR1-sg2

10 52 .5 1.25 0.625 0.313 0.156 0.078

0.078

OVCAR-8 0.039 Vehicle

(day 5)

ML210(M)

PEX3-sg1

PEX10-sg1

200μM

-2 -1 0

0.0

0.5

1.0

1.5

Log 10 (M ML210)

Relative

growth

area

OVCAR-8

sgNC

AGPS-sg 2

FAR1-sg 2

e

-5 -4 -3 -2 -1 0 123

0

2

4

6

Log 2 (PEX3-sg / sgNC)

C36:4 ePE

C42:11 ePE

C38:5 ePEC34:5 ePC

C40:7 ePE

ePE PUFA-TAGs

ePC diacyl-PL

786-O lipidomics

-2 -1 0

0.0

0.5

1.0

1.5

Log 10 (μM RSL3)

Relativ

ev

iabilit

y

-3 -2 -1

0.0

0.5

1.0

1.5

Log 10 (M RSL3)

0.0

0.4

0.8

1.2

l m

-1 -0.5 0

0.0

0.4

0.8

1.2

sgNC

FAR1-sg1 (bulk)

FAR1-sg1 SCC9

Log 10 (M ML210)

Relative

viabilit

y

OVCAR-8

GAPDH

FAR1

sgNCsg1 (bul

k)

sg1 SCC9

j FAR1 sgRNA

-1 -0.5 0

0.0

0.4

0.8

1.2

sgNC

AGPS-sg2 (bulk)

AGPS-sg2 SCC9

Log 10 (M ML210)

Relative

viabilit

y

GAPDH

AGPS

sgNCsg2 (bulk)sg2 SCC9

AGPS sgRNA OVCAR-^8

k

Extended Data Fig. 3 | See next page for caption.