[2014 Fall Life Sciences & IBB Regular Seminar]
     
       
    ▶Subject: Mitochondrial dysfunction and diabetes mellitus
    
    ▶Speaker: Kyong Soo Park, Ph.D. (Seoul National University College of Medicine)
            
    ▶Date: 4:00PM/Oct./24(Fri)/2014
           
    ▶Place: Auditorium(1F), POSTECH Biotech Center
           
            *Abctract
          Mitochondria are powerhouse of cell and produce ATP by oxidative phosphorylation (OXPHOS). Mitochondria are also involved in reactive oxygen species (ROS) generation and apoptotic pathways. There is a growing body of evidence suggesting that mitochondrial dysfunction plays an important role in the pathogenesis of diabetes mellitus. It could impair insulin secretion in pancreatic beta cells as well as insulin action in peripheral tissues. Both genetic and environmental factors could affect mitochondrial function. Among genetic factors, point mutations or large deletion in mitochondrial DNA (mtDNA) are associated with maternally inherited diabetes mellitus. Common polymorphisms in mtDNA and mtDNA haplogoups are also associated with the risk of type 2 diabetes mellitus. Among genetic mutations and variations, the leucyl-tRNAUUR substitution of G for A at nucleotide position 3243(mtDNA 3243 mutation) is the most frequent mutation causing diabetes mellitus. Gene expression profiling of cybrid cells harboring mtDNA 3243 mutation showed decreased expression of OXPHOS protein encoded by nuclear genome as well as mtDNA. Although this mutation may impair aminoacylation of mtDNA encoded proteins, mechanism(s) leading to down-regulation of most of nuclear encoded OXPHOS proteins is unclear. We could identify and experimentally demonstrated ROS-mediated JNK(c-JUN N-terminal kinase)-RXRA(retinoid X receptor α)-PGC1
(peroxisome proliferator-activated receptor γ, coactivator 1 α) retrograde signaling is critical for down-regulation of OXPHOS genes, thereby forming a transcriptional feedback loop that can aggravate reduction of OXPHOS and resulting mitochondrial dysfunctions. These results suggest that altered regulation of RXRA-PGC1 may play an important role in mitochondrial dysfunction associated with mtDNA 3243 mutation.

    ▶Inquiry: Prof. Sung Ho Ryu (279-2292)
          
      * This seminar will be given in English