Mitochondrial Nascent Chain Quality Control Determines Organelle Form and Function

Tutkimustuotos: ArtikkelijulkaisuKatsausartikkeliTieteellinenvertaisarvioitu

Kuvaus

Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in animals is only responsible for synthesis of 1% of the organelle proteome. Because of the relatively small contribution of the mitochondrial genome to the overall proteome, the synthesis and quality control of these nascent chains to maintain organelle proteostasis has long been overlooked. However, recent research has uncovered mechanisms by which defects to the quality control of mitochondrial gene expression are linked to a novel cellular stress response that impinges upon organelle form and function and cell fitness. In this review, we discuss the mechanisms for a key event in the response: activation of the metalloprotease OMA1. This severs the membrane tether of the dynamin-related GTPase OPA1, which is a critical determinant for mitochondrial morphology and function. We also highlight the evolutionary conservation from bacteria of these quality-control mechanisms to maintain membrane integrity, gene expression, and cell fitness.

Alkuperäiskielienglanti
LehtiACS Chemical Biology
Vuosikerta14
Numero11
Sivut2396-2405
Sivumäärä10
ISSN1554-8929
DOI - pysyväislinkit
TilaJulkaistu - marraskuuta 2019
OKM-julkaisutyyppiA2 Katsausartikkeli tieteellisessä aikakauslehdessä

Tieteenalat

  • 1182 Biokemia, solu- ja molekyylibiologia

Lainaa tätä

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title = "Mitochondrial Nascent Chain Quality Control Determines Organelle Form and Function",
abstract = "Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in animals is only responsible for synthesis of 1{\%} of the organelle proteome. Because of the relatively small contribution of the mitochondrial genome to the overall proteome, the synthesis and quality control of these nascent chains to maintain organelle proteostasis has long been overlooked. However, recent research has uncovered mechanisms by which defects to the quality control of mitochondrial gene expression are linked to a novel cellular stress response that impinges upon organelle form and function and cell fitness. In this review, we discuss the mechanisms for a key event in the response: activation of the metalloprotease OMA1. This severs the membrane tether of the dynamin-related GTPase OPA1, which is a critical determinant for mitochondrial morphology and function. We also highlight the evolutionary conservation from bacteria of these quality-control mechanisms to maintain membrane integrity, gene expression, and cell fitness.",
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author = "Brendan Battersby and Uwe Richter and Omid Safronov",
year = "2019",
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doi = "10.1021/acschembio.9b00518",
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Mitochondrial Nascent Chain Quality Control Determines Organelle Form and Function. / Battersby, Brendan; Richter, Uwe; Safronov, Omid.

julkaisussa: ACS Chemical Biology, Vuosikerta 14, Nro 11, 11.2019, s. 2396-2405.

Tutkimustuotos: ArtikkelijulkaisuKatsausartikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Mitochondrial Nascent Chain Quality Control Determines Organelle Form and Function

AU - Battersby, Brendan

AU - Richter, Uwe

AU - Safronov, Omid

PY - 2019/11

Y1 - 2019/11

N2 - Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in animals is only responsible for synthesis of 1% of the organelle proteome. Because of the relatively small contribution of the mitochondrial genome to the overall proteome, the synthesis and quality control of these nascent chains to maintain organelle proteostasis has long been overlooked. However, recent research has uncovered mechanisms by which defects to the quality control of mitochondrial gene expression are linked to a novel cellular stress response that impinges upon organelle form and function and cell fitness. In this review, we discuss the mechanisms for a key event in the response: activation of the metalloprotease OMA1. This severs the membrane tether of the dynamin-related GTPase OPA1, which is a critical determinant for mitochondrial morphology and function. We also highlight the evolutionary conservation from bacteria of these quality-control mechanisms to maintain membrane integrity, gene expression, and cell fitness.

AB - Proteotoxicity has long been considered a key factor in mitochondrial dysfunction and human disease. The origin of the endogenous offending toxic substrates and the regulatory pathways to deal with these insults, however, have remained unclear. Mitochondria maintain a compartmentalized gene expression system that in animals is only responsible for synthesis of 1% of the organelle proteome. Because of the relatively small contribution of the mitochondrial genome to the overall proteome, the synthesis and quality control of these nascent chains to maintain organelle proteostasis has long been overlooked. However, recent research has uncovered mechanisms by which defects to the quality control of mitochondrial gene expression are linked to a novel cellular stress response that impinges upon organelle form and function and cell fitness. In this review, we discuss the mechanisms for a key event in the response: activation of the metalloprotease OMA1. This severs the membrane tether of the dynamin-related GTPase OPA1, which is a critical determinant for mitochondrial morphology and function. We also highlight the evolutionary conservation from bacteria of these quality-control mechanisms to maintain membrane integrity, gene expression, and cell fitness.

KW - AAA PROTEASE

KW - CHAPERONE-LIKE ACTIVITY

KW - FUSION

KW - INNER MEMBRANE

KW - MUTATIONS

KW - OPA1

KW - ORGANIZATION

KW - SPASTIC PARAPLEGIA

KW - STRESS RESPONSES

KW - TURNOVER

KW - 1182 Biochemistry, cell and molecular biology

U2 - 10.1021/acschembio.9b00518

DO - 10.1021/acschembio.9b00518

M3 - Review Article

VL - 14

SP - 2396

EP - 2405

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 11

ER -