Background: Mitochondria are autonomous cellular organelles that oversee a variety of functions such as metabol-ism, energy production, calcium buffering, and cell fate determination. Most recently, MITOCHONDRIAL dysfunction caused by MITOCHONDRIAL mutations played important roles in the pathoGENESis of asthma. However, the frequency of MITOCHONDRIAL tRNA mutations in asthma is largely unknown.Methods: Overall, 200 patients with asthma and 100 healthy control subjects were recruited between Jan 2015 and Dec 2015 at the Guangming New District People's Hospital, Shenzhen, Guangdong Province, China. We first per-formed PCR amplification of the MITOCHONDRIAL tRNA GENES and subsequently sequenced the PCR products, and we used the pathogenicity scoring system to evaluate the potential role of these mutations.Results: Two patients carrying the tRNAThr G15927A mutation, three patients carrying the tRNAAla T5655C muta-tion and one patient carrying the tRNAGlu A14693G mutation, these mutations were absent in healthy controls. More-over, these mutations located at positions highly conserved between different species, and may cause a failure in mito-chondrial tRNA metabolism, consequently result in MITOCHONDRIAL dysfunction that responsible for asthma. In addi-tion, the pathogenicity scoring system showed that these mutations should be regarded as "pathogenic".Conclusion: MITOCHONDRIAL tRNA mutations caused the MITOCHONDRIAL dysfunction may be involved in the pathoge-nesis of asthma. Thus, this study provided novel insight into the molecular mechanism underlying MITOCHONDRIAL tRNA mutations in asthma. Moreover, screening for the MITOCHONDRIAL tRNA mutations was advised for the diagnosis of patients with asthma.

Background: Atherosclerosis is a disease that affects large and medium size arteries in the body that underlies coro-nary heart disease. Several nucleotide changes in MITOCHONDRIAL tRNA GENES have been reported in various diseases. The purpose of the study was to identify hotspot MITOCHONDRIAL tRNA mutations in atherosclerotic patients. Methods: In this case-control study, the variations of ten MITOCHONDRIAL tRNA GENES (about 50%) were investigated in 70 patients from October 2013 and June 2015 suffered from atherosclerosis. The related MITOCHONDRIAL area was am-plified using PCR methid. The mutation analysis was performed by Single Strand Conformational Polymorphism (SSCP) and Restriction Fragment Length Polymorphism (RFLP). All the positive samples were sequenced. Results: We found one novel heteroplasmic mutation (m. 5725T>G) and three reported single nucleotide polymor-phisms (SNPs) previously in other diseases including m. 5568A>G, m. 5711A>G and m. 12308A>G. Conclusion: These tRNA mutations can alter their steady state level and affect the structure of tRNA. The role of MITOCHONDRIAL tRNA mutations in the pathoGENESis of atherosclerosis could potentially be important for the under-standing of MITOCHONDRIAL dysfunction in coronary atherosclerotic plaque formation.

Background: Several recent studies have shown that MITOCHONDRIAL DNA mutations lead to major disabilities and premature death in carriers. More than 150 mutations in human MITOCHONDRIAL DNA (mtDNA) GENES have been associated with a wide spectrum of disorders. Varicocele, one of the causes of infertility in men wherein abnormal inflexion and distension of veins of the pampiniform plexus is observed within spermatic cord, can increase reactive oxygen species (ROS) production in semen and cause oxidative stress and sperm dysfunction in patients. Given that mitochondria are the source of ROS production in cells, the aim of this study was to scan nine MITOCHONDRIAL GENES (MT-COX2, MT-tRNALys, MT-ATP8, MT-ATP6, MT-COX3, MT-tRNAGly, MT-ND3, MT-tRNAArg and MT-ND4L) for mutations in infertile patients with varicocele.Materials and Methods: In this cross-sectional study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing were used to detect and identify point mutations respectively in 9 MITOCHONDRIAL GENES in 72 infertile men with varicocele and 159 fertile men. In brief, the samples showing altered electrophoretic patterns of DNA in the SSCP gel were sent for DNA sequencing to identify the exact nucleotide variation.Results: Ten type nucleotide variants were detected exclusively in MITOCHONDRIAL DNA of infertile men. These include six novel nucleotide changes and four variants previously reported for other disorders.Conclusion: Mutations in MITOCHONDRIAL GENES may affect respiratory complexes in combination with environmental risk factors. Therefore these nucleotide variants probably lead to impaired ATP synthesis and MITOCHONDRIAL function ultimately interfering with sperm motility and infertility.

Objective: Autism results from developmental factors that affect many or all functional brain systems. Brain is one of tissues which are crucially in need of adenosine triphos phate (ATP). Autism is noticeably affected by MITOCHONDRIAL dysfunction which impairs energy metabolism. Considering mutations within ATPase 6, ATPase 8 and tRNA Lys GENES, associated with different neural diseases, and the main role of ATPase 6/8 in energy gen eration, we decided to investigate mutations on these mtDNA-encoded GENES to reveal their roles in autism pathoGENESis.Materials and Methods: In this experimental study, mutation analysis for the mentioned GENES were performed in a cohort of 24 unrelated patients with idiopathic autism by employing amplicon sequencing of mtDNA fragments.Results: In this study, 12 patients (50%) showed point mutations that representa signifi cant correlation between autism and mtDNA variations. Most of the identified substitutions (55.55%) were observed on MT-ATP6, altering some conserved amino acids to other ones which could potentially affect ATPase 6 function. Mutations causing amino acid replacement denote involvement of mtDNA GENES, especially ATPase 6 in autism pathoGENESis.Conclusion: MtDNA mutations in relation with autism could be remarkable to realize an understandable mechanism of pathoGENESis in order to achieve therapeutic solutions.