Mitochondrial protein import: role of certain domains of mitochondrial aspartate aminotransferase

1994 ◽  
pp. 81-85
Author(s):  
S. Giannattasio ◽  
A. Azzariti ◽  
R. A. Vacca ◽  
P. Lattanzio ◽  
R. S. Merafina ◽  
...  
Keyword(s):  
Aspartate Aminotransferase ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Import ◽  
Mitochondrial Aspartate Aminotransferase

scholarly journals Increased levels of the mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol

2021 ◽  
Author(s):  
Anna M. Schlagowski ◽  
Katharina Knöringer ◽  
Sandrine Morlot ◽  
Ana Sáchez Vicente ◽  
Felix Boos ◽  
...  
Keyword(s):  
Protein Import ◽  
Mitochondrial Protein ◽  
Model System ◽  
Model Systems ◽  
Aggregate Formation ◽  
Mitochondrial Protein Import ◽  
Precursor Proteins ◽  
Polyq Protein ◽  
Rate Limiting

AbstractThe formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient material and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but the causalities remained unclear. We used yeast as model system to analyze the relevance of mitochondrial processes for the behavior of an aggregation-prone polyQ protein derived from human huntingtin. Induction of Q97-GFP rapidly leads to insoluble cytosolic aggregates and cell death. Although this aggregation impairs mitochondrial respiration only slightly, it interferes with efficient import of mitochondrial precursor proteins. Mutants in the import component Mia40 are hypersensitive to Q97-GFP. Even more surprisingly, Mia40 overexpression strongly suppresses the formation of toxic Q97-GFP aggregates both in yeast and in human cells. Based on these observations, we propose that the posttranslational import into mitochondria competes with aggregation-prone cytosolic proteins for chaperones and proteasome capacity. Owing to its rate-limiting role for mitochondrial protein import, Mia40 acts as a regulatory component in this competition. This role of Mia40 as dynamic regulator in mitochondrial biogenesis can apparently be exploited to stabilize cytosolic proteostasis. (174/175 words)

The Role of Molecular Chaperones in Mitochondrial Protein Import and Folding

1997 ◽  
pp. 127-193 ◽  
Author(s):  
Michael T. Ryan ◽  
Dean J. Naylor ◽  
Peter B. Høj ◽  
Margaret S. Clark ◽  
Nicholas J. Hoogenraad
Keyword(s):  
Molecular Chaperones ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Import

scholarly journals Reinvestigation of the Requirement of Cytosolic ATP for Mitochondrial Protein Import

2004 ◽  
Vol 279 (19) ◽  
pp. 19464-19470 ◽  
Author(s):  
Takeyoshi Asai ◽  
Takashi Takahashi ◽  
Masatoshi Esaki ◽  
Shuh-ichi Nishikawa ◽  
Kenzo Ohtsuka ◽  
...  
Keyword(s):  
Protein Import ◽  
Atp Hydrolysis ◽  
Mitochondrial Protein ◽  
Mitochondrial Matrix ◽  
Mitochondrial Protein Import ◽  
Precursor Proteins ◽  
Reticulocyte Lysate ◽  
Binding To Mitochondria

Protein import into mitochondria requires the energy of ATP hydrolysis inside and/or outside mitochondria. Although the role of ATP in the mitochondrial matrix in mitochondrial protein import has been extensively studied, the role of ATP outside mitochondria (external ATP) remains only poorly characterized. Here we developed a protocol for depletion of external ATP without significantly reducing the import competence of precursor proteins synthesizedin vitrowith reticulocyte lysate. We tested the effects of external ATP on the import of various precursor proteins into isolated yeast mitochondria. We found that external ATP is required for maintenance of the import competence of mitochondrial precursor proteins but that, once they bind to mitochondria, the subsequent translocation of presequence-containing proteins, but not the ADP/ATP carrier, proceeds independently of external ATP. Because depletion of cytosolic Hsp70 led to a decrease in the import competence of mitochondrial precursor proteins, external ATP is likely utilized by cytosolic Hsp70. In contrast, the ADP/ATP carrier requires external ATP for efficient import into mitochondria even after binding to mitochondria, a situation that is only partly attributed to cytosolic Hsp70.

scholarly journals The intermembrane space domain of mitochondrial Tom22 functions as a trans binding site for preproteins with N-terminal targeting sequences.

1997 ◽  
Vol 17 (11) ◽  
pp. 6574-6584 ◽  
Author(s):  
M Moczko ◽  
U Bömer ◽  
M Kübrich ◽  
N Zufall ◽  
A Hönlinger ◽  
...  
Keyword(s):  
Binding Site ◽  
Outer Membrane ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
Cytosolic Domains ◽  
Import Receptors ◽  
Cis And Trans

Mitochondrial protein import is thought to involve the sequential interaction of preproteins with binding sites on cis and trans sides of the membranes. For translocation across the outer membrane, preproteins first interact with the cytosolic domains of import receptors (cis) and then are translocated through a general import pore, in a process proposed to involve binding to a trans site on the intermembrane space (IMS) side. Controversial results have been reported for the role of the IMS domain of the essential outer membrane protein Tom22 in formation of the trans site. We show with different mutant mitochondria that a lack of the IMS domain only moderately reduces the direct import of preproteins with N-terminal targeting sequences. The dependence of import on the IMS domain of Tom22 is significantly enhanced by removing the cytosolic domains of import receptors or by performing import in two steps, i.e., accumulation of a preprotein at the outer membrane in the absence of a membrane potential (delta psi) and subsequent import after reestablishment of a delta psi. After the removal of cytosolic receptor domains, two-step import of a cleavable preprotein strictly requires the IMS domain. In contrast, preproteins with internal targeting information do not depend on the IMS domain of Tom22. We conclude that the negatively charged IMS domain of Tom22 functions as a trans binding site for preproteins with N-terminal targeting sequences, in agreement with the acid chain hypothesis of mitochondrial protein import.

scholarly journals Role of Mitochondrial Protein Import in Age-Related Neurodegenerative and Cardiovascular Diseases

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3528
Author(s):  
Andrey Bogorodskiy ◽  
Ivan Okhrimenko ◽  
Dmitrii Burkatovskii ◽  
Philipp Jakobs ◽  
Ivan Maslov ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cell Survival ◽  
Protein Import ◽  
Fundamental System ◽  
State Of The Art ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Import ◽  
Age Related

Mitochondria play a critical role in providing energy, maintaining cellular metabolism, and regulating cell survival and death. To carry out these crucial functions, mitochondria employ more than 1500 proteins, distributed between two membranes and two aqueous compartments. An extensive network of dedicated proteins is engaged in importing and sorting these nuclear-encoded proteins into their designated mitochondrial compartments. Defects in this fundamental system are related to a variety of pathologies, particularly engaging the most energy-demanding tissues. In this review, we summarize the state-of-the-art knowledge about the mitochondrial protein import machinery and describe the known interrelation of its failure with age-related neurodegenerative and cardiovascular diseases.

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