Mitochondrial DNA

Mitochondria

-eukaryotic organelle that synthesis chemical energy via aerobic repiration (op% of cell’s ATP)

Double Membrane

Composed of outer membrane and a highly folded inner membrane (cristae)

Mitochondrial Matrix

The central fluid-filled space containing enzymes, ribosomes, and their own mitochondrial DNA (mtDNA)

Dynamics

Mitochondria are very dynamic, constantly changing shape, dividing, and fusing together

-depends on demand of the cell

Mitochondria energy production

-Tricarboxylic Acid cycle (TCA), Krebs cycle

-makes ATP

-Electron transport chain: key to energy generation, O2 is required

Mitochondrial ROS/Apoptosis

-is the main source of reactive oxygen species

-Mitochondria can initiate cell death

Mitochondrial DNA (mtDNA)

-mtDNA contains 16569 bp

-Encodes 37 genes:

13 gene coded for proteins all to ETC

2 genes for rRNA

22 genes for transfer RNA (tRNA)

-Transcription in controlled by nDNA

mtDNA promoter area

-Mitochondrial has only one promoter area, the D-loop

-nucleus encoded proteins control mtDNA transcription and replication

-Mitochondrial transcription factor A (TFAM) and DNA polymerase gamma (POLG) control transcription and replication

mtDNA replication/transcription

-For mtDNA stop codons are AGA, AAG

-UGA codes for tryptophan

-Initiation codon for AUA

-mtDNA transcripts all genes each time

Mitochondrial DNA inherited

-Nuclear DNA is inherited from all ancestors

-Mitochondrial DNA i inherited from a single lineage

Mitochondria DNA repais

-mtDNA: relying on nuclear-encoded enzymes to repair damage

-Base excision repair (BER): the primary pathway for oxidative lesions

-8-oxoguanine DNA glycosylase-1 (OGG1): removes 7,8-dihydro-8-oxoguanine (8-oxoG), a common oxidative DNA lesion caused by high ROS in mitochondria

-Single strand break repair (SSBR) mismatch repair (MMR)

mtDNA damage

mtDNA is more prone to damage than nuclear DNA (nDNA) primarily due to:

-its close proximity to reactive oxygen species (ROS) produced during oxidative phophorylation

-lack of protective histones

-limited repair mechanisms compared to nDNA

-any problem in chaperon protein or repair mechanism will affect mitochondrial DNA