Protein translocation into mammalian mitochondria and its role in the development of human mitochondrial disorders

2004 ◽  
pp. 201-225
Author(s):  
Sabine Hofmann ◽  
Matthias F. Bauer
Keyword(s):  
Protein Translocation ◽  
Mitochondrial Disorders ◽  
Mammalian Mitochondria

scholarly journals Mitochondria and Eye

2021 ◽  
Author(s):  
Lata Singh ◽  
Mithalesh Kumar Singh
Keyword(s):  
Nuclear Dna ◽  
Protein Complexes ◽  
Critical Role ◽  
Mitochondrial Disorders ◽  
Treatment Modalities ◽  
Renal Tubules ◽  
Metabolic Demand ◽  
Mammalian Mitochondria ◽  
Ocular Disorders

Mitochondria are essential subcellular organelles and important key regulators of metabolism. Mammalian mitochondria contain their own DNA (mtDNA). Human mtDNA is remarkably small (16,569 bp) compared to nuclear DNA. Mitochondria promote aerobic respiration, an important part of energy metabolism in eukaryotes, as the site of oxidative phosphorylation (OXPHOS). OXPHOS occurs in the inner membrane of the mitochondrion and involves 5 protein complexes that sequentially undergo reduction-oxygen reactions ultimately producing adenosine triphosphate (ATP). Tissues with high metabolic demand such as lungs, central nervous system, peripheral nerves, heart, adrenal glands, renal tubules and the retina are affected preferentially by this critical role in energy production by mitochondrial disorders. Eye-affected mitochondrial disorders are always primary, but the role of mitochondrial dysfunction is now best understood in acquired chronic progressive ocular diseases. Recent advances in mitochondrial research have improved our understanding of ocular disorders. In this chapter, we will discuss the mitochondria in relation to eye diseases, ocular tumors, pathogenesis, and treatment modalities that will help to improve the outcomes of these conditions.

scholarly journals The human mitochondrial import receptor, hTom20p, prevents a cryptic matrix targeting sequence from gaining access to the protein translocation machinery.

1996 ◽  
Vol 134 (2) ◽  
pp. 307-313 ◽  
Author(s):  
H M McBride ◽  
I S Goping ◽  
G C Shore
Keyword(s):  
Outer Membrane ◽  
Protein Translocation ◽  
Mitochondrial Outer Membrane ◽  
Mammalian Mitochondria ◽  
Precursor Proteins ◽  
Targeting Signal ◽  
Signal Anchor ◽  
Positively Charged ◽  
Import Receptor

Yeast Mas70p and NADH cytochrome b5 reductase are bitopic integral proteins of the mitochondrial outer membrane and are inserted into the lipid-bilayer in an Nin-Ccyto orientation via an NH2-terminal signal-anchor sequence. The signal anchor of both proteins is comprised of a short, positively charged domain followed by the predicted transmembrane segment. The positively charged domain is capable of functioning independently as a matrix-targeting signal in yeast mitochondria in vitro but does not support import into mammalian mitochondria (rat or human). Rather, this domain represents a cryptic signal that can direct import into mammalian mitochondria only if proximal components of the outer membrane import machinery are removed. This can be accomplished either by treating the surface of the intact mitochondria with trypsin or by generating mitoplasts. The import receptor Tom20p (Mas20p/MOM19) is responsible for excluding the cryptic matrix-targeting signal from mammalian mitochondria since replacement of yeast Tom20p with the human receptor confers this property to the yeast organelle while at the same time maintaining import of other proteins. In addition to contributing to positive recognition of precursor proteins, therefore, the results suggest that hTom20p may also have the ability to screen potential matrix-targeting sequences and exclude certain proteins that would otherwise be recognized and imported by distal components of the outer and inner membrane protein-translocation machinery. These findings also indicate, however, that cryptic signals, if they exist within otherwise native precursor proteins, may remain topogenically silent until the precursor successfully clears hTom20p, at which time the activity of the cryptic signal is manifested and can contribute to subsequent translocation and sorting of the polypeptide.

Primary mitochondrial disorders and diabetes mellitus - two case reports

2018 ◽  
Author(s):  
Lucia Fadiga ◽  
Joana Saraiva ◽  
Diana Oliveira ◽  
Adriana Lages ◽  
Mara Ventura ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Case Reports ◽  
Mitochondrial Disorders

Spatial localization of unknown proteins in the endoplasmic reticulum predicts functions

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Michael D. Jain ◽  
Hisao Nagaya ◽  
Annalyn Gilchrist ◽  
Miroslaw Cygler ◽  
John J.M. Bergeron
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Protein Function ◽  
Protein Translocation ◽  
Spatial Localization ◽  
Predict Protein Function ◽  
Insight Into ◽  
Soluble Fractions ◽  
Er Membrane

Protein synthesis, folding and degradation functions are spatially segregated in the endoplasmic reticulum (ER) with respect to the membrane and the ribosome (rough and smooth ER). Interrogation of a proteomics resource characterizing rough and smooth ER membranes subfractionated into cytosolic, membrane, and soluble fractions gives a spatial map of known proteins involved in ER function. The spatial localization of 224 identified unknown proteins in the ER is predicted to give insight into their function. Here we provide evidence that the proteomics resource accurately predicts the function of new proteins involved in protein synthesis (nudilin), protein translocation across the ER membrane (nicalin), co-translational protein folding (stexin), and distal protein folding in the lumen of the ER (erlin-1, TMX2). Proteomics provides the spatial localization of proteins and can be used to accurately predict protein function.

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