GTPBP8 plays a role in mitoribosome formation in human mitochondria

Miriam Cipullo; Genís Valentín Gesé; Shreekara Gopalakrishna; Annika Krueger; Vivian Lobo; Maria A. Pirozhkova; James Marks; Petra Páleníková; Dmitrii Shiriaev; Yong Liu; Jelena Misic; Yu Cai; Minh Duc Nguyen; Abubakar Abdelbagi; Xinping Li; Michal Minczuk; Markus Hafner; Daniel Benhalevy; Aishe A. Sarshad; Ilian Atanassov; B. Martin Hällberg; Joanna Rorbach

doi:10.1038/s41467-024-50011-x

GTPBP8 plays a role in mitoribosome formation in human mitochondria

Miriam Cipullo, Genís Valentín Gesé, Shreekara Gopalakrishna, Annika Krueger, Vivian Lobo, Maria A. Pirozhkova, James Marks, Petra Páleníková, Dmitrii Shiriaev, Yong Liu, Jelena Misic, Yu Cai, Minh Duc Nguyen, Abubakar Abdelbagi, Xinping Li, Michal Minczuk, Markus Hafner, Daniel Benhalevy, Aishe A. Sarshad, Ilian AtanassovB. Martin Hällberg, Joanna Rorbach^*

^*Corresponding author for this work

The Shmunis School of Biomedicine and Cancer Research

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Mitochondrial gene expression relies on mitoribosomes to translate mitochondrial mRNAs. The biogenesis of mitoribosomes is an intricate process involving multiple assembly factors. Among these factors, GTP-binding proteins (GTPBPs) play important roles. In bacterial systems, numerous GTPBPs are required for ribosome subunit maturation, with EngB being a GTPBP involved in the ribosomal large subunit assembly. In this study, we focus on exploring the function of GTPBP8, the human homolog of EngB. We find that ablation of GTPBP8 leads to the inhibition of mitochondrial translation, resulting in significant impairment of oxidative phosphorylation. Structural analysis of mitoribosomes from GTPBP8 knock-out cells shows the accumulation of mitoribosomal large subunit assembly intermediates that are incapable of forming functional monosomes. Furthermore, fPAR-CLIP analysis reveals that GTPBP8 is an RNA-binding protein that interacts specifically with the mitochondrial ribosome large subunit 16 S rRNA. Our study highlights the role of GTPBP8 as a component of the mitochondrial gene expression machinery involved in mitochondrial large subunit maturation.

Original language	English
Article number	5664
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-50011-x
State	Published - Dec 2024

Funding

Funders	Funder number
Max Planck Instituut voor Psycholinguïstiek
Karolinska Institutet
Knut och Alice Wallenbergs Stiftelse	2018.0080, KAW 2017.0080, KAW 2018.0080, WAF2017
European Molecular Biology Organization	LTF-2020-606
Vetenskapsrådet	VR2016-02179

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-024-50011-x

Cite this

Cipullo, M., Valentín Gesé, G., Gopalakrishna, S., Krueger, A., Lobo, V., Pirozhkova, M. A., Marks, J., Páleníková, P., Shiriaev, D., Liu, Y., Misic, J., Cai, Y., Nguyen, M. D., Abdelbagi, A., Li, X., Minczuk, M., Hafner, M., Benhalevy, D., Sarshad, A. A., ... Rorbach, J. (2024). GTPBP8 plays a role in mitoribosome formation in human mitochondria. Nature Communications, 15(1), Article 5664. https://doi.org/10.1038/s41467-024-50011-x

@article{d1baead19b9042a199f53785a990f16e,

title = "GTPBP8 plays a role in mitoribosome formation in human mitochondria",

abstract = "Mitochondrial gene expression relies on mitoribosomes to translate mitochondrial mRNAs. The biogenesis of mitoribosomes is an intricate process involving multiple assembly factors. Among these factors, GTP-binding proteins (GTPBPs) play important roles. In bacterial systems, numerous GTPBPs are required for ribosome subunit maturation, with EngB being a GTPBP involved in the ribosomal large subunit assembly. In this study, we focus on exploring the function of GTPBP8, the human homolog of EngB. We find that ablation of GTPBP8 leads to the inhibition of mitochondrial translation, resulting in significant impairment of oxidative phosphorylation. Structural analysis of mitoribosomes from GTPBP8 knock-out cells shows the accumulation of mitoribosomal large subunit assembly intermediates that are incapable of forming functional monosomes. Furthermore, fPAR-CLIP analysis reveals that GTPBP8 is an RNA-binding protein that interacts specifically with the mitochondrial ribosome large subunit 16 S rRNA. Our study highlights the role of GTPBP8 as a component of the mitochondrial gene expression machinery involved in mitochondrial large subunit maturation.",

author = "Miriam Cipullo and \{Valent{\'i}n Ges{\'e}\}, Gen{\'i}s and Shreekara Gopalakrishna and Annika Krueger and Vivian Lobo and Pirozhkova, \{Maria A.\} and James Marks and Petra P{\'a}len{\'i}kov{\'a} and Dmitrii Shiriaev and Yong Liu and Jelena Misic and Yu Cai and Nguyen, \{Minh Duc\} and Abubakar Abdelbagi and Xinping Li and Michal Minczuk and Markus Hafner and Daniel Benhalevy and Sarshad, \{Aishe A.\} and Ilian Atanassov and H{\"a}llberg, \{B. Martin\} and Joanna Rorbach",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-50011-x",

language = "אנגלית",

volume = "15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Cipullo, M, Valentín Gesé, G, Gopalakrishna, S, Krueger, A, Lobo, V, Pirozhkova, MA, Marks, J, Páleníková, P, Shiriaev, D, Liu, Y, Misic, J, Cai, Y, Nguyen, MD, Abdelbagi, A, Li, X, Minczuk, M, Hafner, M, Benhalevy, D, Sarshad, AA, Atanassov, I, Hällberg, BM & Rorbach, J 2024, 'GTPBP8 plays a role in mitoribosome formation in human mitochondria', Nature Communications, vol. 15, no. 1, 5664. https://doi.org/10.1038/s41467-024-50011-x

TY - JOUR

T1 - GTPBP8 plays a role in mitoribosome formation in human mitochondria

AU - Cipullo, Miriam

AU - Valentín Gesé, Genís

AU - Gopalakrishna, Shreekara

AU - Krueger, Annika

AU - Lobo, Vivian

AU - Pirozhkova, Maria A.

AU - Marks, James

AU - Páleníková, Petra

AU - Shiriaev, Dmitrii

AU - Liu, Yong

AU - Misic, Jelena

AU - Cai, Yu

AU - Nguyen, Minh Duc

AU - Abdelbagi, Abubakar

AU - Li, Xinping

AU - Minczuk, Michal

AU - Hafner, Markus

AU - Benhalevy, Daniel

AU - Sarshad, Aishe A.

AU - Atanassov, Ilian

AU - Hällberg, B. Martin

AU - Rorbach, Joanna

PY - 2024/12

Y1 - 2024/12

N2 - Mitochondrial gene expression relies on mitoribosomes to translate mitochondrial mRNAs. The biogenesis of mitoribosomes is an intricate process involving multiple assembly factors. Among these factors, GTP-binding proteins (GTPBPs) play important roles. In bacterial systems, numerous GTPBPs are required for ribosome subunit maturation, with EngB being a GTPBP involved in the ribosomal large subunit assembly. In this study, we focus on exploring the function of GTPBP8, the human homolog of EngB. We find that ablation of GTPBP8 leads to the inhibition of mitochondrial translation, resulting in significant impairment of oxidative phosphorylation. Structural analysis of mitoribosomes from GTPBP8 knock-out cells shows the accumulation of mitoribosomal large subunit assembly intermediates that are incapable of forming functional monosomes. Furthermore, fPAR-CLIP analysis reveals that GTPBP8 is an RNA-binding protein that interacts specifically with the mitochondrial ribosome large subunit 16 S rRNA. Our study highlights the role of GTPBP8 as a component of the mitochondrial gene expression machinery involved in mitochondrial large subunit maturation.

AB - Mitochondrial gene expression relies on mitoribosomes to translate mitochondrial mRNAs. The biogenesis of mitoribosomes is an intricate process involving multiple assembly factors. Among these factors, GTP-binding proteins (GTPBPs) play important roles. In bacterial systems, numerous GTPBPs are required for ribosome subunit maturation, with EngB being a GTPBP involved in the ribosomal large subunit assembly. In this study, we focus on exploring the function of GTPBP8, the human homolog of EngB. We find that ablation of GTPBP8 leads to the inhibition of mitochondrial translation, resulting in significant impairment of oxidative phosphorylation. Structural analysis of mitoribosomes from GTPBP8 knock-out cells shows the accumulation of mitoribosomal large subunit assembly intermediates that are incapable of forming functional monosomes. Furthermore, fPAR-CLIP analysis reveals that GTPBP8 is an RNA-binding protein that interacts specifically with the mitochondrial ribosome large subunit 16 S rRNA. Our study highlights the role of GTPBP8 as a component of the mitochondrial gene expression machinery involved in mitochondrial large subunit maturation.

UR - http://www.scopus.com/inward/record.url?scp=85197677872&partnerID=8YFLogxK

U2 - 10.1038/s41467-024-50011-x

DO - 10.1038/s41467-024-50011-x

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 38969660

AN - SCOPUS:85197677872

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5664

ER -

GTPBP8 plays a role in mitoribosome formation in human mitochondria

Abstract

Funding

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this