Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

Hope Isobel I Needs; Margherita  Protasoni; Jeremy M Henley; Julien  Prudent; Ian R Collinson; Gonçalo C. Pereira

doi:10.3390/life11050432

Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

Hope Isobel I Needs
, Margherita Protasoni
, Jeremy M Henley
, Julien Prudent
, Ian R Collinson^*
, Gonçalo C. Pereira^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease

Original language	English
Article number	432
Number of pages	44
Journal	Life
Volume	11
Issue number	5
DOIs	https://doi.org/10.3390/life11050432
Publication status	Published - 11 May 2021

Bibliographical note

Funding Information:
HN is supported by the Wellcome Trust Dynamic Molecular Cell Biology PhD programme (215317/Z/19/Z). MP is recipient of an MRC funded PhD scholarship. Research in JMH laboratory is supported the BBSRC (BB/R00787X/1), Wellcome Trust Investigator Award (220799/Z/20/Z), and Leverhulme Trust (RPG-2019-191). Research in the JP laboratory is supported by the Medical Research Council, UK (MC_UU_00015/7). Research in the IC laboratory is supported by the Wellcome Trust: Investigator Award (104632/Z/14/Z). GCP is supported by the Swiss National Science Foundation (Synergia project CRSII5_180326). The APC was funded by University of Bristol Open Access via IC.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Research Groups and Themes

Bristol BioDesign Institute

Keywords

protein import
mitochondrial dysfunction
respiratory complex assembly
supercomplexes
neurodegeneration
mitochondrial proteostasis

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title = "Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration",

abstract = "The fact that >99\% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease",

keywords = "protein import, mitochondrial dysfunction, respiratory complex assembly, supercomplexes, neurodegeneration, mitochondrial proteostasis",

author = "Needs, \{Hope Isobel I\} and Margherita Protasoni and Henley, \{Jeremy M\} and Julien Prudent and Collinson, \{Ian R\} and \{C. Pereira\}, Gon{\c c}alo",

note = "Funding Information: HN is supported by the Wellcome Trust Dynamic Molecular Cell Biology PhD programme (215317/Z/19/Z). MP is recipient of an MRC funded PhD scholarship. Research in JMH laboratory is supported the BBSRC (BB/R00787X/1), Wellcome Trust Investigator Award (220799/Z/20/Z), and Leverhulme Trust (RPG-2019-191). Research in the JP laboratory is supported by the Medical Research Council, UK (MC\_UU\_00015/7). Research in the IC laboratory is supported by the Wellcome Trust: Investigator Award (104632/Z/14/Z). GCP is supported by the Swiss National Science Foundation (Synergia project CRSII5\_180326). The APC was funded by University of Bristol Open Access via IC. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Collinson, Ian R

AU - C. Pereira, Gonçalo

N1 - Funding Information: HN is supported by the Wellcome Trust Dynamic Molecular Cell Biology PhD programme (215317/Z/19/Z). MP is recipient of an MRC funded PhD scholarship. Research in JMH laboratory is supported the BBSRC (BB/R00787X/1), Wellcome Trust Investigator Award (220799/Z/20/Z), and Leverhulme Trust (RPG-2019-191). Research in the JP laboratory is supported by the Medical Research Council, UK (MC_UU_00015/7). Research in the IC laboratory is supported by the Wellcome Trust: Investigator Award (104632/Z/14/Z). GCP is supported by the Swiss National Science Foundation (Synergia project CRSII5_180326). The APC was funded by University of Bristol Open Access via IC. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease

AB - The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease

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Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration

Abstract

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