• Circuitry and regulatory mechanisms Of Mitochondria
  • Ramtin Naderian,1,*
    1. Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran


  • Introduction: Mitochondria are the major source of energy for the cellular activity, by ATP generation via oxidative phosphorylation. Emerging evidence of the last decade indicates that mitochondria form a highly dynamic intracellular network that executes the “quality control” of the organelle's population in a process that implies their fusion, fission and autophagic degradation (known as ‘mitophagy’). Mitochondria regulate the operation of intracellular signalling cascades, generate reactive oxygen species (ROS), execute fatty acids β‐oxidation, participate in aminoacid metabolism, pyridine synthesis, phospholipid modifications, calcium regulation and cells survival, senescence and death. The homeostasis of any healthy cell implies also a controlled regulation of mitochondrial mass and function, as an adaptive response to safeguard the mitochondrial (mt) DNA and to meet the energy demands vital for cellular function.
  • Methods: The present study was conducted by systematic review. To access the Circuitry and regulatory mechanisms of Mitochondrial genomic and energy transduction machinery, articles indexed in databases Science Direct, PubMed, Scopus, Google scholar, web of science, Embase and Medline were used over 2018 to 2021. According to the defined criteria, finally 17 Full text articles were reviewed in this study.
  • Results: Transcriptional networks Transcription of the mitochondrial genome occurs bidirectionally from the L-strand promoter and H-strand promoter located on opposing mtDNA strands at OH and produces a polycistronic transcript spanning nearly the entire length of the mitochondrial genome A widely accepted model for the assembly of the mitochondrial transcription initiation complex maintains that mitochondrial transcription factor A (TFAM) interacts via its C terminus with mitochondrial transcription factor B2 (TFB2M) and subsequently recruits mitochondrial RNA polymerase (POLMRT) to the promoter region. MITOCHONDRIAL BIOGENESIS MACHINERY Mitochondrial biogenesis is a complex process. Indeed, mitochondria are organelles that harbor their own genome (mtDNA). In mammalian cells, mtDNA is a circular molecule, which encodes for 13 mRNAs, 22 tRNAs, and 2 rRNAs. All 13 mRNAs of mtDNA encode 11 subunits of the ETC complexes I, III and IV, and 2 subunits of ATP synthase (complex V). Mitochondrial biogenesis is regulated at the transcriptional level, by nuclear proteins. The main actor of this process is a transcription complex composed of four proteins that belong to the same family: heme activator proteins (Hap) 2, 3, 4, and 5 Hap2p, Hap3p, and Hap5p form a complex that is bound to nuclear DNA, and Hap4p is the co-activator of this complex, a functional homolog of peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1 (PGC-1α, see below). Hence, activity of the overall complex is mostly dependent on Hap4p. The HAP complex regulates the expression of genes encoding several proteins such as proteins of the Krebs cycle or proteins of the OXPHOS system. Mitochondrial genes expression depends on the RNA polymerase Rpo41 and its accessory transcription factor Mtf1 The process of mitochondrial biogenesis takes place mainly in healthy cells. Interesting, in cancerous cells enhanced oxidative phosphorylation and mitochondrial biogenesis were correlated with invasion and metastasis
  • Conclusion: Mitochondria are not static organelles but are mobile and dynamic. Recent findings provide evidence of direct connections and communication between mitochondria as well
  • Keywords: Mitochondrial genomic, energy transduction, MITOCHONDRIAL BIOGENESIS, Transcriptional networks