Immunoproteasome-specific subunit PSMB9 induction is required to regulate cellular proteostasis upon mitochondrial dysfunction.

Perturbed cellular protein homeostasis (proteostasis) and mitochondrial dysfunction play an important role in neurodegenerative diseases, however, the interplay between these two phenomena remains unclear. Mitochondrial dysfunction leads to a delay in mitochondrial protein import, causing accumulation of non-imported mitochondrial proteins in the cytosol and challenging proteostasis. Cells respond by increasing proteasome activity and molecular chaperones in yeast and C.

The ubiquitin-proteasome system and its crosstalk with mitochondria as therapeutic targets in medicine.

The ubiquitin-proteasome system constitutes a major pathway for protein degradation in the cell. Therefore the crosstalk of this pathway with mitochondria is a major topic with direct relevance to many mitochondrial diseases. Proteasome dysfunction triggers not only protein toxicity, but also mitochondrial dysfunction.

Testosterone increases apoptotic cell death and decreases mitophagy in Leber's hereditary optic neuropathy cells.

Leber's hereditary optic neuropathy (LHON) is one of the most common mitochondrial diseases caused by point mutations in mitochondrial DNA (mtDNA). The majority of diagnosed LHON cases are caused by a point mutation at position 11,778 in the mitochondrial genome. LHON mainly affects young men in their 20s and 30s with usually poor visual prognosis.

Analysis of BNIP3 and BNIP3L/Nix expression in cybrid cell lines harboring two LHON-associated mutations.

Mitochondria are key players in cell death through the activation of the intrinsic apoptosis pathway. BNIP3 and BNIP3L/Nix are outer mitochondrial membrane bifunctional proteins which because of containing both BH3 and LIR domains play a role in cellular response to stress by regulation of apoptosis and selective autophagy. Leber's Hereditary Optic Neuropathy (LHON) is the most common mitochondrial disease in adults, characterized by painless loss of vision caused by atrophy of the optic nerve.

Mitochondrial DNA in pediatric leukemia patients.

Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy.

Investigating Leber's hereditary optic neuropathy: Cell models and future perspectives.

Leber's hereditary optic neuropathy (LHON) was the first human disease found to be associated with a mitochondrial DNA (mtDNA) point mutation. The most common LHON mutations are 11778G>A, 3460G>A or 14484T>C. The most common clinical features of LHON are optic nerve and retina atrophy.

Changing phenotypic expression in a patient with a mitochondrial encephalopathy due to 13042G>A de novo mutation--a 5 year follow up.

Mutations in NADH dehydrogenase (ND) subunits of complex I lead to mitochondrial encephalomyopathies associated with various phenotypes. This report aims to present the patient's clinical symptomatology in the context of a very rare 13042G>A de novo mutation and with an emphasis on changing phenotypic expression and pronounced, long-standing response to levetiracetam.

m.3635G>A mutation as a cause of Leber hereditary optic neuropathy.

Over 90% of Leber's hereditary optic neuropathy (LHON) is caused by one of three mtDNA mutations (m.11778A>G, m.3460G>A, m.

[Population data analysis of miniSTR loci: D10S1248, D14S1434 and D22S1045 in the Pomerania-Kujawy region of Poland].

This paper presents the allele frequencies and forensic parameters of the three miniSTR loci D10S1248, D14S1434 and D22S1045 in the Pomerania-Kujawy region of Poland. Genomic DNA was extracted by a standard phenol-chloroform extraction procedure. The three miniSTR loci D10S1248, D14S1434 and D22S1045 were amplified in a triplex polymerase chain reaction with the primer sets designed by Coble and Butler in a GeneAmp PCR System 9700 (Applied Biosystems).

Genotype-phenotype correlations in Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON), acute or subacute vision loss due to retinal ganglion cell death which in the long run leads to optic nerve atrophy is one of the most widely studied maternally inherited diseases caused by mutations in mitochondrial DNA. Although three common mutations, 11778G>A, 14484T>C or 3460G>A are responsible for over 90% of cases and affect genes encoding complex I subunits of the respiratory chain, their influence on bioenergetic properties of the cell is marginal and cannot fully explain the pathology of the disease. The following chain of events was proposed, based on biochemical and anatomical properties of retinal ganglion cells whose axons form the optic nerve: mitochondrial DNA mutations increase reactive oxygen species production in these sensitive cells, leading to caspase-independent apoptosis.