Peroxisomes are juxtaposed to strategic sites on mitochondria.
Peroxisomes are ubiquitous and dynamic organelles that house many important pathways of cellular metabolism. In recent years it has been demonstrated that mitochondria are tightly connected with peroxisomes and are defective in several peroxisomal diseases. Indeed, these two organelles share metabolic routes as well as resident proteins and, at least in mammals, are connected via a vesicular transport pathway. However the exact extent of cross-talk between peroxisomes and mitochondria remains unclear. Here we used a combination of high throughput genetic manipulations of yeast libraries alongside high content screens to systematically unravel proteins that affect the transport of peroxisomal proteins and peroxisome biogenesis. Follow up work on the effector proteins that were identified revealed that peroxisomes are not randomly distributed in cells but are rather localized to specific mitochondrial subdomains such as mitochondria-ER junctions and sites of acetyl-CoA synthesis. Our approach highlights the intricate geography of the cell and suggests an additional layer of organization as a possible way to enable efficient metabolism. Our findings pave the way for further studying the machinery aligning mitochondria and peroxisomes, the role of the juxtaposition, as well as its regulation during various metabolic conditions. More broadly, the approaches used here can be easily applied to study any organelle of choice, facilitating the discovery of new aspects in cell biology.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. yael.elbaz@weizmann.ac.il einat.zalckvar@weizmann.ac.il maya.schuldiner@weizmann.ac.il.
Yifat
Y
Cohen
Yoel Alexander
YA
Klug
Lazar
L
Dimitrov
Zohar
Z
Erez
Silvia G
SG
Chuartzman
Dalia
D
Elinger
Ido
I
Yofe
Kareem
K
Soliman
Jutta
J
Gärtner
Sven
S
Thoms
Randy
R
Schekman
Yael
Y
Elbaz-Alon
Einat
E
Zalckvar
Maya
M
Schuldiner
D000105:Acetyl Coenzyme A / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D016296:Mutagenesis; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins; D000105:Acetyl Coenzyme A