MitoRibo-Tag Mice Provide a Tool for In Vivo Studies of Mitoribosome Composition

Busch, J.; Cipullo, M.; Atanassov, I.; Bratic, A.; Ramos, E.S.; Schöndorf, T.; Li, X.; Pearce, S. F.; Milenkovic, D.; Rorbach, J.; Larsson, N.G.

doi:10.1016/j.celrep.2019.09.080

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MitoRibo-Tag Mice Provide a Tool for In Vivo Studies of Mitoribosome Composition

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Busch, J.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons281607

Cipullo, M.
Rorbach – Mitochondrial Gene Expression, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons104734

Atanassov, I.
Proteomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129386

Bratic, A.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129414

Ramos, E.S.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons281639

Schöndorf, T.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons277927

Li, X.
Proteomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons281605

Pearce, S. F.
Rorbach – Mitochondrial Gene Expression, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129408

Milenkovic, D.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons276040

Rorbach, J.
Rorbach – Mitochondrial Gene Expression, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons129342

Larsson, N.G.
Department Larsson - Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/31693908
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Citation

Busch, J., Cipullo, M., Atanassov, I., Bratic, A., Ramos, E., Schöndorf, T., et al. (2019). MitoRibo-Tag Mice Provide a Tool for In Vivo Studies of Mitoribosome Composition. Cell Rep, 29(6), 1728-1738 e9. doi:10.1016/j.celrep.2019.09.080.

Cite as: https://hdl.handle.net/21.11116/0000-000B-4322-3

Abstract

Mitochondria harbor specialized ribosomes (mitoribosomes) necessary for the synthesis of key membrane proteins of the oxidative phosphorylation (OXPHOS) machinery located in the mitochondrial inner membrane. To date, no animal model exists to study mitoribosome composition and mitochondrial translation coordination in mammals in vivo. Here, we create MitoRibo-Tag mice as a tool enabling affinity purification and proteomics analyses of mitoribosomes and their interactome in different tissues. We also define the composition of an assembly intermediate formed in the absence of MTERF4, necessary for a late step in mitoribosomal biogenesis. We identify the orphan protein PUSL1, which interacts with a large subunit assembly intermediate, and demonstrate that it is an inner-membrane-associated mitochondrial matrix protein required for efficient mitochondrial translation. This work establishes MitoRibo-Tag mice as a powerful tool to study mitoribosomes in vivo, enabling future studies on the mitoribosome interactome under different physiological states, as well as in disease and aging.