A Role for the Mitochondrial Protein Mrpl44 in Maintaining OXPHOS Capacity

Janet H C Yeo; Jarrod P J Skinner; Matthew J Bird; Luke E Formosa; Jian-Guo Zhang; Ruth M Kluck; Gabrielle T Belz; Mark M W Chong

doi:10.1371/journal.pone.0134326

A Role for the Mitochondrial Protein Mrpl44 in Maintaining OXPHOS Capacity

PLoS One. 2015 Jul 29;10(7):e0134326. doi: 10.1371/journal.pone.0134326. eCollection 2015.

Authors

Janet H C Yeo¹, Jarrod P J Skinner², Matthew J Bird³, Luke E Formosa⁴, Jian-Guo Zhang⁵, Ruth M Kluck⁵, Gabrielle T Belz⁵, Mark M W Chong⁶

Affiliations

¹ Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; St. Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
² St. Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
³ Murdoch Childrens Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville VIC, Australia.
⁴ Department of Biochemistry, La Trobe University, Bundoora, VIC, Australia.
⁵ Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
⁶ St. Vincent's Institute of Medical Research, Fitzroy, VIC, Australia; Department of Medicine (St Vincent's), University of Melbourne, Parkville VIC, Australia.

Abstract

We identified Mrpl44 in a search for mammalian proteins that contain RNase III domains. This protein was previously found in association with the mitochondrial ribosome of bovine liver extracts. However, the precise Mrpl44 localization had been unclear. Here, we show by immunofluorescence microscopy and subcellular fractionation that Mrpl44 is localized to the matrix of the mitochondria. We found that it can form multimers, and confirm that it is part of the large subunit of the mitochondrial ribosome. By manipulating its expression, we show that Mrpl44 may be important for regulating the expression of mtDNA-encoded genes. This was at the level of RNA expression and protein translation. This ultimately impacted ATP synthesis capability and respiratory capacity of cells. These findings indicate that Mrpl44 plays an important role in the regulation of the mitochondrial OXPHOS capacity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / biosynthesis
Animals
Cattle
Cell Line
DNA, Mitochondrial / genetics
DNA, Mitochondrial / metabolism
Gene Expression Regulation
Gene Knockdown Techniques
HEK293 Cells
Humans
Mice
Mitochondria, Liver / metabolism
Mitochondrial Proteins / chemistry
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism*
Mitochondrial Ribosomes / metabolism
NIH 3T3 Cells
Oxidative Phosphorylation
Oxygen Consumption
Protein Multimerization
Ribonuclease III / chemistry
Ribonuclease III / genetics
Ribonuclease III / metabolism
Ribosomal Proteins / chemistry
Ribosomal Proteins / genetics
Ribosomal Proteins / metabolism

Substances

DNA, Mitochondrial
Mitochondrial Proteins
Ribosomal Proteins
Adenosine Triphosphate
Ribonuclease III

Grants and funding

This work was funded by grants from the National Health and Medical Research Council, Australia (#1004541 and #1042211 to MMWC; #1042582 to GTB; #1016647 to JGZ), MMWC is an Australian Research Council QEII Fellow, GTB is an Australian Research Council Future Fellow, JHCY was supported by the Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship. This work was made possible through Victorian State Government Operational Infrastructure Support, Australian National Health and Medical Research Council Research Institute Infrastructure Support Scheme and the Australian Mitochondrial Disease Foundation.