As result of their evolutionary history, mitochondria possess their own genome.~2 billion years ago anaerobic proto- eukaryotic cells engulfed aerobic protobacteria at a time of increasing atmospheric oxygen. The resulting mutual beneficial endosymbiosis created mitochondria and resulted in a radical change in cellular metabolism that was now able to oxidize metabolic substrates to generate high-energy carriers much more efficiently. All eukaryotic cells (besides mature erythrocytes) have mitochondria or modified remnants of mitochondria (some parasites). Complen Compler Compier Compies Human mitochondrial (mt) DNA consists of 1 circular chromosome with 16,569 base pairs encoding 37 genes (2 FRNA, 22 tRNA, 13 MRNA). It is organized differently from nuclear DNA; it lacks histones/nucleosomes. Compare: hu chromosome 1 alone 247 million bp, ~4,200 genes. (don't memorize #s except: 13 protein genes + others genes) •The 13 proteins encoded by mtDNA are synthesized by special mito ribosomes. •Each of these 13 proteins are components of the oxidative phosphorylation complexes (respiratory chain) (colored, on left). They are especially hydrophobic and thus it would be very expensive to import them from the cytosol. ~70 other proteins of the OXPHOS system are encoded by the nuclear genome (gray, on left). •Like prokaryotes, mitochondria generate RNA transcripts that encode multiple genes (polycistronic transcripts) that are then processed into individual MRNA or tRNA transcripts for translation. •Although many essential genes needed by mitochondria and chloroplasts are no longer encoded by their respective DNAS these genes are not lost. These genes were integrated into the nuclear genome. The degree to which this happened differs among Jeukaryotes, and presumably this process is continuing. 100, Suncn Fun NADH NAD ADP. NDI NDS Don't study details ND4 NDAL CO ATPase CO About 1,500 mt proteins are encoded by nuclear DNA, synthesized by cytosolic ribosomes and imported into mitochondria. Protein levels must be balanced!!! How this is accomplished is being studied. Suggest a molecular mechanism that could control protein levels so they match to form functional machineries. •Mitochondrial reproduction is unrelated to cell division. mtDNA mutations and diseases are almost always maternally inherited (why?), unchanged, meaning: without recombination. crros 2 copies TOCHOMORON 1000's copies•mtDNA may be more likely to acquire mutations than nuclear DNA (think of 2 possible reasons) •mtDNA heteroplasmy (different mtDNA in same cell) and somatic segregation (diff mtDNA in diff cells) lead to different mt genotypes in cells of the same organism. In patients with inherited mtDNA mutations, most mutations are heteroplasmic and proportion of mutant mtDNA varies among tissues. Tissues with high oxidative rates such as CNS, heart/skeletal muscle are most sensitive to mt defects. Drawing on left misleading. rather: mutant and non mut mt DNA at different ratio in the mito network