Genome organisation of Mitochondria.pptx

Genome organisation of Mitochondria

1. Dr. Manikandan Kathirvel M.Sc., Ph.D., (NET) Assistant Professor, Department of Life Sciences, Kristu Jayanti College (Autonomous), Reaccredited with "A++" Grade by NAAC K. Narayanapura , Kothanur (PO) Bengaluru   Genome Organisation of Mitochondria

2. Mitochondria and its genome Mitochondria  play a central role in cellular energy provision. The organelles contain their own  genome  with a modified genetic code. Mitochondria are thought to be derived from eubacterial endosymbionts b ecause they have their own DNA and the machinery for gene expression. The mitochondrial genomes of the three major kingdoms, Animalia , Eukaryomycota and Plantae , have different characters. The size of mitochondrial genomes of fungi is in the range 17–176 kb . The mitochondrial genomes of fungi encode a few more genes than those of animals. But the main reason for the variety in size is not differences in coding capacities but the sizes of introns and spacer regions. The size of plant mitochondrial genomes is extremely variable. It ranges from 16 to 2400 kb. The variety of gene content and molecular structure and the variation of the length of spacer regions and introns are the major characteristics of plant mitochondrial genomes.

3. MITOCHONDRIAL DNA( mt dna ) in humans The human mitochondrial genome is a circular DNA molecule of about 16 kilobases . It encodes 37 genes: 13 genes encoding for subunits of respiratory complexes I, III, IV and V, 22 genes for mitochondrial tRNA (for the 20 standard amino acids, plus an extra gene for leucine and serine), and 2 genes for rRNA. 3. One mitochondrion can contain two to ten copies of its DNA. The size of animal mitochondrial genomes ranges mostly between 16 and 19 kb and they do not contain introns . The human  mitochondrial  DNA ( mtDNA ) is a double-stranded, circular molecule of 16,569 bp and contains 37 genes coding for two rRNAs , 22 tRNAs and 13 polypeptides.

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5. Nuclear genes control the mitochondria biogenesis . Nuclear-encoded genes are necessary for the expression of mitochondrial genes, including transcription, pre-mRNA processing, translation of the mRNAs into mitochondrial proteins, the assembly of ribosomes and respiratory complexes, and are also required for the targeting and degradation of organellar subunits. 

6. Mitochondrial ribosome: structure and assembly The mitoribosome consists of a large 39S subunit ( mtLSU ) and a small 28S ( mtSSU ) subunit. Compared with the bacterial ribosome, the mammalian mitoribosome has reduced rRNA components. To compensate for this, 36 mitochondria-specific proteins have been recruited to the ribosome, primarily found at the periphery of the complex surrounding a highly conserved catalytic core.

7. Mitochondrial DNA replication – D loop Model The mitochondrial genome is a circle, 16.6 kb of DNA. The two strands are notably different in base composition, leading to one strand being “heavy” (the H strand) and the other light (the L strand). Both strands encode genes, although more are on the H strand. The D loop is also the site where most of replication and transcription is controlled.

8. Transcription in human mitochondria is driven by a DNA-dependant RNA polymerase called POLRMT, which is structurally similar to RNA polymerases in T3 and T7 bacteriophages . This includes high sequence homology to the C-terminal catalytic core of the enzyme. At the N-terminal domain, POLRMT also contains two pentatricopeptide repeat (PPR) domains, commonly found in RNA-associated proteins, where they are required for site-specific interactions. The initiation of transcription requires the association of POLRMT with mitochondrial transcription factor A (TFAM) and mitochondrial transcription factor B2 (TFB2M). TFAM is a DNA-binding protein, which, in addition to transcription activation, also packages DNA in the nucleoid . TFB2M, the key function of this protein is DNA melting during the initiation of transcription. Almost the entire mitochondrial genome is transcribed as long polycistronic transcripts.

9. Mitochondrial Translation Mitochondrial translation is fully dependent on various nuclear-encoded regulatory proteins. In the mammalian mitochondria, the mitochondrial initiation factors, mtIF2 and mtIF3, control the initiation of translation. Elongation of translation is mediated by mitochondrial elongation factors, EFTu (TUFM), EFTs (TSFM) and EFGM (GFM1). Termination of mitochondrial translation is finally triggered by the presence of a stop codon at the A-site. Four mitochondrial proteins with homology to ribosome release factors have been identified in humans, including mtRF1, mtRF1a, C12orf65 and ICT1.

10. Mitochondrial transcription and translation – Summary Progression of mitochondrial transcription and translation requires the sequential recruitment of different, nuclear-encoded initiation, elongation and termination factors. Almost the entire mitochondrial genome is transcribed as long polycistronic transcripts. Maturation of the transcripts requires endonucleolytic cleavage, but not all mRNAs are produced through RNase P and RNase Z function. Mitochondrial mRNA steady-state levels are mainly controlled post-transcriptionally. The role mitochondrial mRNA polyadenylation is not fully understood. Mitochondrial tRNAs undergo extensive chemical modifications, including the addition and removal of nucleotides during their maturation. Aminoacyl tRNA- synthetases charge tRNAs with their cognate amino acid ( A  cognate amino acid  pairs with the tRNA that has the appropriate anticodon ; a non- cognate amino acid  does not). Mammalian mitoribosomes differ considerably from other ribosomes as far as architecture and composition are concerned. The assembly of the mitoribosome assembly pathway is likely to be considerably different from its bacterial counterpart , implying the presence of mitochondria-specific regulatory factors.