Mutant mtDNA at 1555 A to G in 12S rRNA Gene and Hypersusceptibility of Mitochondrial Translation to Streptomycin Can Be Co-Transferred to ρ0HeLa Cells

Inoue, Kimiko; Takai, Daiya; Soejima, Aki; Isobe, Kotoyo; Yamasoba, Tatsuya; Oka, Yoshitomo; Goto, Yu‐ichi; Hayashi, Jun‐Ichi

doi:10.1006/bbrc.1996.0923

Cited by 55 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This substitution is also found in a streptomycin-resistant strain of Mycobacterium tuberculosis (52). Furthermore, A1555 in human mitochondrial 12 S rRNA has been considered to confer a certain degree of aminoglycoside resistance on the mitoribosome by reducing binding activity (53,54). Thus, the mammalian mitoribosome has potential resistance to aminoglycoside antibiotics.…”

Section: Fig 4-continuedmentioning

confidence: 99%

Proteomic Analysis of the Mammalian Mitochondrial Ribosome

Suzuki¹,

Terasaki²,

Takemoto-Hori³

et al. 2001

Journal of Biological Chemistry

137

View full text Add to dashboard Cite

The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits. In the previous study, we analyzed 39 S large subunit proteins from bovine mitoribosome (Suzuki, T., Terasaki, M., Takemoto-Hori, C., Hanada, T., Ueda, T., Wada, A., and Watanabe, K. (2001) J. Biol. Chem. 276, 21724-21736). The results suggested structural compensation for the rRNA deficit through proteins of increased molecular mass in the mitoribosome. We report here the identification of 28 S small subunit proteins. Each protein was separated by radical-free high-reducing two-dimensional polyacrylamide gel electrophoresis and analyzed by liquid chromatography/mass spectrometry/mass spectrometry using electrospray ionization/ion trap mass spectrometer to identify cDNA sequence by expressed sequence tag data base searches in silico. Twenty one proteins from the small subunit were identified, including 11 new proteins along with their complete cDNA sequences from human and mouse. In addition to these proteins, three new proteins were also identified in the 55 S mitoribosome. We have clearly identified a mitochondrial homologue of S12, which is a key regulatory protein of translation fidelity and a candidate for the autosomal dominant deafness gene, DFNA4. The apoptosis-related protein DAP3 was found to be a component of the small subunit, indicating a new function for the mitoribosome in programmed cell death. In summary, we have mapped a total of 55 proteins from the 55 S mitoribosome on the two-dimensional polyacrylamide gels.

show abstract

Section: Fig 4-continuedmentioning

confidence: 99%

Proteomic Analysis of the Mammalian Mitochondrial Ribosome

Suzuki¹,

Terasaki²,

Takemoto-Hori³

et al. 2001

Journal of Biological Chemistry

137

View full text Add to dashboard Cite

show abstract

“…It has been reported that the use of linezolid resulted in low levels of mitochondrial translational products and lactic acidosis associated with A2706G as well as G3010A mutations, in addition to other side effects [86]. Streptomycin administration linked with G1555A mutation results in ototoxicity and deafness [89]. Further, clozapine treatment may give rise to increased production of pro-inflammatory cytokines involved in inflammation, which in turn is associated with alterations in mitochondrial function and obesity [95] (Table 1, 2).…”

Section: Mitochondrial Dna Mutations Associated With Antibioticsmentioning

confidence: 99%

“…Accumulating evidence has highlighted that the use of aminoglycosides such as streptomycin, gentamycin, neomycin, kanamycin, etc., either in high doses or for extended periods, potentially results in nephrotoxicity, ototoxicity, and hearing loss. The sensitivity of mutations associated with hearing loss and deafness in mitochondria, such as m. 1555A>G [89], m. 1494C>T [90,91], m. 1095T>C [92], m. 827A>G [93], m. 1645C>G, m. 3243A>G, and m. 961A>G, to aminoglycosides, indicates their role in inducing the phenotype in Chinese and Spanish populations [86,94].…”

Section: Mitochondrial Dna Mutations Associated With Antibioticsmentioning

confidence: 99%

Antibiotics-Induced Obesity: A Mitochondrial Perspective

Andrade

Jayaprakash

Bhat

et al. 2017

Public Health Genomics

View full text Add to dashboard Cite

Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity. Apart from the involvement of biosocial causes influencing diet, physical activity, and antibiotic use, pathogenesis of obesity is linked to interconnected functional alterations in cells, tissues and organs due to biochemical, epigenetic and genetic factors. Mitochondrial dysfunction is one such factor, which is becoming the primary focus of various aspects of research on multifactorial complex diseases and is providing new perspectives on etiology, biomarker-based diagnosis, and drug sensitivity. Through this review, we have made an attempt to present the interplay between use of antibiotics, obesity, and associated mitochondrial dysfunction. This may provide insights into the molecular basis, genetic predisposition and environmental triggers, which in turn may have potential clinical applications in the management of antibiotic use.

show abstract

“…(2) The phenotype of sensoneural hearing loss or deafness due to aminoglycoside toxicity is the same as that found in most mitochondrial encephalomyopathies, suggesting mitochondrial involvement [106]. (3) Mitochondrial DNA from individuals with the A1555G polymorphism can be cotransfected into r 0 HeLa cells, which lack mitochondrial DNA altogether, causing these cells to become sensitive to streptomycin intoxication [107]. (4) Significant uptake of tritium-labeled aminoglycosides has been observed in proximal tubular kidney cells and within sensory hair cells, with significant localization to mitochondria [108].…”

Section: Aminoglycoside Toxicitymentioning

confidence: 97%

Therapeutic Agents Acting on RNA Targets

Rife

2010

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

There are many therapeutics that target RNA, such as streptomycin, gentamicin, and tetracycline; some of them have been in existence for many years. All of them bind to ribosomal RNA and alter normal ribosome function. The modern strategies of drug discovery and design pertain nearly exclusively to protein targets. However, the field of drug discovery for RNA targets is maturing rapidly, largely due to the exciting ribosome/drug complexes that have recently been solved. Potential RNA drug targets abound for bacterial, viral, and cellular systems. Nevertheless, questions remain as to whether or not compounds can be found that simultaneously satisfy RNA binding and pharmacological properties, such as absorption and membrane permeation. The range of interactions observed, from Coulombic to hydrophobic, and the predicted “drug‐like” qualities of several ribosome binding antibiotics, suggest that the discovery of drugs that target RNA can be a general phenomenon.

show abstract

Mutant mtDNA at 1555 A to G in 12S rRNA Gene and Hypersusceptibility of Mitochondrial Translation to Streptomycin Can Be Co-Transferred to ρ0HeLa Cells

Cited by 55 publications

References 0 publications

Proteomic Analysis of the Mammalian Mitochondrial Ribosome

Proteomic Analysis of the Mammalian Mitochondrial Ribosome

Antibiotics-Induced Obesity: A Mitochondrial Perspective

Therapeutic Agents Acting on RNA Targets

Contact Info

Product

Resources

About