Human Disorders

Cell organelle Double membrane bound Found in all nucleated cells Principal generators of cellular ATP by oxidative phosphorylation (OXPHOS)

Consists of: Electron transferring respiratory chain (complexes I IV) ATP Synthase (Complex V)

Mitochondria consist of their own DNA Extra-chromosomal DNA mtDNA / mitochondrial genome

mtDNA

False color transmission electron micrograph (TEM) of circular DNA from a mitochondrioncircular DNA molecules 5-6 micrometers long, molecular weight of around 10 million; 3 to 6 copies/mitochondrian coding capacity of about 5,000 amino acids needs to rely on a supplement of external DNA (from the cell nucleus) Magnification: X 150,000 at 35mm size.

It takes about 3000 genes to make a mitochondrion mtDNA encodes only 37 of these The rest is encoded by the nuclear genome

Only ~3% of the genes necessary to make a mitochondrion (100 of the 3000) are allocated for making ATP More than 95% (2900 of 3000) are involved with other functions tied to the specialized duties of the differentiated cell in which it resides

Pyrimidine biosynthesis Heme biosynthesis Specialized to detoxify ammonia in the urea cycle Cholesterol metabolism Estrogen and testosterone synthesis Neurotransmitter metabolism Free radical production and detoxification

Mitochondria are involved in all these functions in addition to breaking down (oxidizing) the fat, protein and carbohydrates that we consume

Extremely small compared to the nuclear genome Multicopy Circular dsDNA molecule 16.6 kb

Encodes: 13 essential polypeptides of the OXPHOS system RNA machinery (2 rRNAs and 22 tRNAs)

Remaining protein subunits that make up the respiratory-chain complexes, those required for mtDNA maintenance are encoded by the nuclear genome These are synthesized on cytoplasmic ribosomes and are specifically targeted and sorted to their correct location within the organelle

mtDNA mutations are an important cause of inherited disease