Contractile activity-induced adaptations in the mitochondrial protein import system

1998 ◽  
Vol 274 (5) ◽  
pp. C1380-C1387 ◽  
Author(s):  
Mark Takahashi ◽  
Alan Chesley ◽  
Damien Freyssenet ◽  
David A. Hood
Keyword(s):  
Outer Membrane ◽  
Malate Dehydrogenase ◽  
Mitochondrial Biogenesis ◽  
Protein Import ◽  
Contractile Activity ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Import ◽  
The Matrix ◽  
Stimulating Factor ◽  
Import Receptor

We previously demonstrated that subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial subfractions import proteins at different rates. This study was undertaken to investigate 1) whether protein import is altered by chronic contractile activity, which induces mitochondrial biogenesis, and 2) whether these two subfractions adapt similarly. Using electrical stimulation (10 Hz, 3 h/day for 7 and 14 days) to induce contractile activity, we observed that malate dehydrogenase import into the matrix of the SS and IMF mitochondia isolated from stimulated muscle was significantly increased by 1.4- to 1.7-fold, although the pattern of increase differed for each subfraction. This acceleration of import may be mitochondrial compartment specific, since the import of Bcl-2 into the outer membrane was not affected. Contractile activity also modified the mitochondrial content of proteins comprising the import machinery, as evident from increases in the levels of the intramitochondrial chaperone mtHSP70 as well as the outer membrane import receptor Tom20 in SS and IMF mitochondria. Addition of cytosol isolated from stimulated or control muscles to the import reaction resulted in similar twofold increases in the ability of mitochondria to import malate dehydrogenase, despite elevations in the concentration of mitochondrial import-stimulating factor within the cytosol of chronically stimulated muscle. These results suggest that chronic contractile activity modifies the extra- and intramitochondrial environments in a fashion that favors the acceleration of precursor protein import into the matrix of the organelle. This increase in protein import is likely an important adaptation in the overall process of mitochondrial biogenesis.

scholarly journals Mitochondrial assembly: protein import

2004 ◽  
Vol 63 (2) ◽  
pp. 293-300 ◽  
Author(s):  
David A. Hood ◽  
Anna-Maria Joseph
Keyword(s):  
Molecular Chaperones ◽  
Mammalian Cells ◽  
Protein Import ◽  
Contractile Activity ◽  
Mitochondrial Protein ◽  
Energy Status ◽  
Mitochondrial Protein Import ◽  
Physiological Importance ◽  
The Matrix ◽  
Import Receptors

The protein import process of mitochondria is vital for the assembly of the hundreds of nuclear-derived proteins into an expanding organelle reticulum. Most of our knowledge of this complex multisubunit network comes from studies of yeast and fungal systems, with little information known about the protein import process in mammalian cells, particularly skeletal muscle. However, growing evidence indicates that the protein import machinery can respond to changes in the energy status of the cell. In particular, contractile activity, a powerful inducer of mitochondrial biogenesis, has been shown to alter the stoichiometry of the protein import apparatus via changes in several protein import machinery components. These adaptations include the induction of cytosolic molecular chaperones that transport precursors to the matrix, the up-regulation of outer membrane import receptors, and the increase in matrix chaperonins that facilitate the import and proper folding of the protein for subsequent compartmentation in the matrix or inner membrane. The physiological importance of these changes is an increased capacity for import into the organelle at any given precursor concentration. Defects in the protein import machinery components have been associated with mitochondrial disorders. Thus, contractile activity may serve as a possible mechanism for up-regulation of mitochondrial protein import and compensation for mitochondrial phenotype alterations observed in diseased muscle.

scholarly journals Structural Basis of Presequence Recognition by the Mitochondrial Protein Import Receptor Tom20

Cell ◽  
2000 ◽  
Vol 100 (5) ◽  
pp. 551-560 ◽  
Author(s):  
Yoshito Abe ◽  
Toshihiro Shodai ◽  
Takanori Muto ◽  
Katsuyoshi Mihara ◽  
Hisayoshi Torii ◽  
...  
Keyword(s):  
Protein Import ◽  
Mitochondrial Protein ◽  
Structural Basis ◽  
Mitochondrial Protein Import ◽  
Import Receptor

scholarly journals Inactivation of the Neurospora crassa gene encoding the mitochondrial protein import receptor MOM19 by the technique of "sheltered RIP".

Genetics ◽  
1994 ◽  
Vol 136 (1) ◽  
pp. 107-118 ◽  
Author(s):  
T A Harkness ◽  
R L Metzenberg ◽  
H Schneider ◽  
R Lill ◽  
W Neupert ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Target Gene ◽  
Protein Import ◽  
Selectable Marker ◽  
Mitochondrial Protein ◽  
Mutant Gene ◽  
Mitochondrial Protein Import ◽  
Gene Encoding ◽  
Precursor Proteins ◽  
Import Receptor

Abstract We have used a technique referred to as "sheltered RIP" (repeat induced point mutation) to create mutants of the mom-19 gene of Neurospora crassa, which encodes an import receptor for nuclear encoded mitochondrial precursor proteins. Sheltered RIP permits the isolation of a mutant gene in one nucleus, even if that gene is essential for the survival of the organism, by sheltering the nucleus carrying the mutant gene in a heterokaryon with an unaffected nucleus. Furthermore, the nucleus harboring the RIPed gene contains a selectable marker so that it is possible to shift nuclear ratios in the heterokaryons to a state in which the nucleus containing the RIPed gene predominates in cultures grown under selective conditions. This results in a condition where the target gene product should be present at very suboptimal levels and allows the study of the mutant phenotype. One allele of mom-19 generated by this method contains 44 transitions resulting in 18 amino acid substitutions. When the heterokaryon containing this allele was grown under conditions favoring the RIPed nucleus, no MOM19 protein was detectable in the mitochondria of the strain. Homokaryotic strains containing the RIPed allele exhibit a complex and extremely slow growth phenotype suggesting that the product of the mom-19 gene is important in N. crassa.

scholarly journals Evolution of mitochondrial protein import – lessons from trypanosomes

2020 ◽  
Vol 401 (6-7) ◽  
pp. 663-676 ◽  
Author(s):  
André Schneider
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Protein Import ◽  
Outer Membrane Proteins ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
System A ◽  
Import Receptors ◽  
Inner Membrane Protein

AbstractThe evolution of mitochondrial protein import and the systems that mediate it marks the boundary between the endosymbiotic ancestor of mitochondria and a true organelle that is under the control of the nucleus. Protein import has been studied in great detail in Saccharomyces cerevisiae. More recently, it has also been extensively investigated in the parasitic protozoan Trypanosoma brucei, making it arguably the second best studied system. A comparative analysis of the protein import complexes of yeast and trypanosomes is provided. Together with data from other systems, this allows to reconstruct the ancestral features of import complexes that were present in the last eukaryotic common ancestor (LECA) and to identify which subunits were added later in evolution. How these data can be translated into plausible scenarios is discussed, providing insights into the evolution of (i) outer membrane protein import receptors, (ii) proteins involved in biogenesis of α-helically anchored outer membrane proteins, and (iii) of the intermembrane space import and assembly system. Finally, it is shown that the unusual presequence-associated import motor of trypanosomes suggests a scenario of how the two ancestral inner membrane protein translocases present in LECA evolved into the single bifunctional one found in extant trypanosomes.

Multiple pathways for mitochondrial protein traffic

2009 ◽  
Vol 390 (8) ◽  
Author(s):  
Toshiya Endo ◽  
Koji Yamano
Keyword(s):  
Outer Membrane ◽  
Protein Trafficking ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
Inner Membrane ◽  
Protein Traffic

Abstract Mitochondria are two-membrane bounded organelles consisting of 1000–2000 different proteins, most of which are synthesized in the cytosol and subsequently imported into mitochondria. The imported proteins are further sorted to one of the four compartments, the outer membrane, intermembrane space, inner membrane, and matrix, mostly following one of the five major pathways. Mitochondrial protein import and sorting are mediated by the translocator complexes in the membranes and chaperones in the aqueous compartments operating along the import pathways. Here, we summarize the expanding knowledge on the roles of translocators, chaperones, and related components in the multiple pathways for mitochondrial protein trafficking.

scholarly journals Tim23–Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import

2009 ◽  
Vol 184 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Yasushi Tamura ◽  
Yoshihiro Harada ◽  
Takuya Shiota ◽  
Koji Yamano ◽  
Kazuaki Watanabe ◽  
...  
Keyword(s):  
Motor Proteins ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
Inner Membrane ◽  
The Matrix ◽  
General Protein ◽  
Mitochondrial Hsp70

Mitochondrial protein traffic requires coordinated operation of protein translocator complexes in the mitochondrial membrane. The TIM23 complex translocates and inserts proteins into the mitochondrial inner membrane. Here we analyze the intermembrane space (IMS) domains of Tim23 and Tim50, which are essential subunits of the TIM23 complex, in these functions. We find that interactions of Tim23 and Tim50 in the IMS facilitate transfer of precursor proteins from the TOM40 complex, a general protein translocator in the outer membrane, to the TIM23 complex. Tim23–Tim50 interactions also facilitate a late step of protein translocation across the inner membrane by promoting motor functions of mitochondrial Hsp70 in the matrix. Therefore, the Tim23–Tim50 pair coordinates the actions of the TOM40 and TIM23 complexes together with motor proteins for mitochondrial protein import.

scholarly journals The peptidases involved in plant mitochondrial protein import

2019 ◽  
Vol 70 (21) ◽  
pp. 6005-6018 ◽  
Author(s):  
Abi S Ghifari ◽  
Shaobai Huang ◽  
Monika W Murcha
Keyword(s):  
Mitochondrial Biogenesis ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Import ◽  
Mitochondrial Proteome ◽  
Encoded Proteins

Mitochondrial biogenesis requires correct targeting and import of nuclear-encoded proteins to ensure the mitochondrial proteome responds to meet the plant’s energetic demands. Protein-degrading machineries also play key roles in protein import and mitochondrial biogenesis.

scholarly journals From cytosol to mitochondria: the beginning of a protein journey

2020 ◽  
Vol 401 (6-7) ◽  
pp. 645-661 ◽  
Author(s):  
Maria Clara Avendaño-Monsalve ◽  
José Carlos Ponce-Rojas ◽  
Soledad Funes
Keyword(s):  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Protein Import ◽  
Protein Targeting ◽  
Mitochondrial Protein ◽  
Past Research ◽  
Membrane Receptors ◽  
Mitochondrial Proteins ◽  
Mitochondrial Protein Import ◽  
The Past

AbstractMitochondrial protein import is one of the key processes during mitochondrial biogenesis that involves a series of events necessary for recognition and delivery of nucleus-encoded/cytosol-synthesized mitochondrial proteins into the organelle. The past research efforts have mainly unraveled how membrane translocases ensure the correct protein sorting within the different mitochondrial subcompartments. However, early steps of recognition and delivery remain relatively uncharacterized. In this review, we discuss our current understanding about the signals on mitochondrial proteins, as well as in the mRNAs encoding them, which with the help of cytosolic chaperones and membrane receptors support protein targeting to the organelle in order to avoid improper localization. In addition, we discuss recent findings that illustrate how mistargeting of mitochondrial proteins triggers stress responses, aiming to restore cellular homeostasis.

scholarly journals Assembly of the Mitochondrial Protein Import Channel

2010 ◽  
Vol 21 (18) ◽  
pp. 3106-3113 ◽  
Author(s):  
Thomas Becker ◽  
Bernard Guiard ◽  
Nicolas Thornton ◽  
Nicole Zufall ◽  
David A. Stroud ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Membrane Insertion ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Protein Import ◽  
Transmembrane Segments ◽  
Tom Complex ◽  
Assembly Pathway ◽  
Assembly Defect

The preprotein translocase of the outer mitochondrial membrane (TOM) consists of a central β-barrel channel, Tom40, and six proteins with α-helical transmembrane segments. The precursor of Tom40 is imported from the cytosol by a pre-existing TOM complex and inserted into the outer membrane by the sorting and assembly machinery (SAM). Tom40 then assembles with α-helical Tom proteins to the mature TOM complex. The outer membrane protein Mim1 promotes membrane insertion of several α-helical Tom proteins but also affects the biogenesis of Tom40 by an unknown mechanism. We have identified a novel intermediate in the assembly pathway of Tom40, revealing a two-stage interaction of the precursor with the SAM complex. The second SAM stage represents assembly of Tom5 with the precursor of Tom40. Mim1-deficient mitochondria accumulate Tom40 at the first SAM stage like Tom5-deficient mitochondria. Tom5 promotes formation of the second SAM stage and thus suppresses the Tom40 assembly defect of mim1Δ mitochondria. We conclude that the assembly of newly imported Tom40 is directly initiated at the SAM complex by its association with Tom5. The involvement of Mim1 in Tom40 biogenesis can be largely attributed to its role in import of Tom5.

Sign in / Sign up

Export Citation Format

Share Document