Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin-dependent membrane organizing proteins.

Serricchio, Mauro; Vissa, Adriano; Kim, Peter K; Yip, Christopher M; McQuibban, G Angus (2018). Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin-dependent membrane organizing proteins. Biochimica and biophysica acta - molecular and cell biology of lipids, 1863(4), pp. 447-457. Elsevier 10.1016/j.bbalip.2018.01.007

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The mitochondrial glycerophospholipid cardiolipin plays important roles in mitochondrial biology. Most notably, cardiolipin directly binds to mitochondrial proteins and helps assemble and stabilize mitochondrial multi-protein complexes. Despite their importance for mitochondrial health, how the proteins involved in cardiolipin biosynthesis are organized and embedded in mitochondrial membranes has not been investigated in detail. Here we show that human PGS1 and CLS1 are constituents of large protein complexes. We show that PGS1 forms oligomers and associates with CLS1 and PTPMT1. Using super-resolution microscopy, we observed well-organized nanoscale structures formed by PGS1. Together with the observation that cardiolipin and CLS1 are not required for PGS1 to assemble in the complex we predict the presence of a PGS1-centered cardiolipin-synthesizing scaffold within the mitochondrial inner membrane. Using an unbiased proteomic approach we found that PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS components MIC60 and MIC19. We further mapped the protein-protein interaction sites between PGS1 and itself, CLS1, MIC60 and PHB. Overall, this study provides evidence for the presence of a cardiolipin synthesis structure that transiently interacts with cardiolipin-dependent protein complexes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Serricchio, Mauro

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1388-1981

Publisher:

Elsevier

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

20 Feb 2019 10:14

Last Modified:

03 Nov 2019 00:39

Publisher DOI:

10.1016/j.bbalip.2018.01.007

PubMed ID:

29343430

Uncontrolled Keywords:

CLS1 Cardolipin MICOS Mitochondria PGS1 Prohibitin

BORIS DOI:

10.7892/boris.125037

URI:

https://boris.unibe.ch/id/eprint/125037

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