Mitochondrial DNA & Mitochondrial Diseases – Core Vocabulary

A comprehensive set of vocabulary flashcards covering mitochondrial DNA structure, replication, genetic code variants, inheritance patterns, damage mechanisms, and hallmark mitochondrial diseases.

Mitochondrial DNA (mtDNA)

A 16,569-bp double-stranded circular genome with 37 genes (13 protein-coding, 22 tRNA, 2 rRNA) housed in each mitochondrion.

Heavy strand (H-strand)

The guanine-rich mtDNA strand that encodes 28 genes and has its own promoter (HSP).

Light strand (L-strand)

The cytosine-rich mtDNA strand that encodes 9 genes and has a separate promoter (LSP).

D-loop

Non-coding control region where mtDNA transcription and replication are initiated; does NOT code respiratory chain polypeptides.

OH (Origin of Heavy-strand replication)

Specific site in the D-loop where synthesis of the heavy strand begins.

OL (Origin of Light-strand replication)

Replication start point for the light strand, located ~two-thirds around the mtDNA circle from OH.

Polycistronic transcription

Process in which each mtDNA strand is transcribed as a long RNA that is later cleaved into individual mRNAs, rRNAs, and tRNAs.

DNA polymerase γ (POLG)

The sole DNA polymerase responsible for mtDNA replication and repair.

TFAM (Transcription Factor A, Mitochondrial)

Protein that packages mtDNA and regulates both its transcription and replication.

POLRMT

Mitochondrial RNA polymerase that synthesizes RNA from mtDNA templates.

Asynchronous replication

Replication mode in which the two mtDNA strands replicate at different times from distinct origins (OH and OL).

Strand-displacement model

Mechanism describing asymmetric, bidirectional mtDNA replication where one strand temporarily displaces the other.

Maternal inheritance

Transmission pattern in which all offspring receive mtDNA exclusively from the mother; affected males cannot pass mutations to children.

Homoplasmy

State in which all mtDNA copies within a cell are identical (all normal or all mutant).

Heteroplasmy

Coexistence of wild-type and mutant mtDNA in the same cell, creating variable mutant loads.

Threshold effect

Concept that clinical disease appears only when the proportion of mutant mtDNA exceeds a critical level.

Mitochondrial genetic code

Variant code where several codon assignments differ from the universal code (e.g., UGA = Trp).

UGA codon (mtDNA)

Encodes tryptophan instead of a stop signal in mitochondria.

AUA codon (mtDNA)

Reads as methionine—one of two start codons in mitochondria (with AUG).

AGA / AGG codons (mtDNA)

Function as stop codons rather than coding arginine in mitochondrial translation.

Oxidative phosphorylation (OXPHOS)

Process by which mitochondrial respiratory complexes I–V generate ATP using electrons and a proton gradient.

Complex I mtDNA-encoded subunits

ND1, ND2, ND3, ND4, ND4L, ND5, ND6 proteins of NADH:ubiquinone oxidoreductase.

Complex III mtDNA-encoded subunit

Cytochrome b protein of the cytochrome bc1 complex.

Complex IV mtDNA-encoded subunits

COX1, COX2, and COX3 proteins of cytochrome c oxidase.

Complex V mtDNA-encoded subunits

ATP6 and ATP8 proteins of ATP synthase.

Mitochondrial DNA damage

High mutation rate due to ROS exposure, lack of histone protection, and less-efficient repair systems.

Mitochondrial disease

Disorder caused by defects in mitochondrial respiratory chain components encoded by mtDNA or nuclear DNA.

MELAS

Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like episodes; presents with stroke-like episodes <40 yrs, seizures, myopathy.

LHON

Leber Hereditary Optic Neuropathy; sudden painless bilateral vision loss, typically in young males.

MERRF

Myoclonic Epilepsy with Ragged Red Fibers; characterized by myoclonus, epilepsy, and ataxia.

Kearns-Sayre syndrome (KSS)

Multisystem mtDNA deletion disorder with ophthalmoplegia, pigmentary retinopathy, and heart block.

Leigh syndrome

Subacute necrotizing encephalomyopathy causing progressive neurodegeneration and respiratory chain failure in infancy/childhood.

Ragged red fibers

Aggregates of abnormal mitochondria at the muscle fiber periphery visualized by Gomori trichrome stain in many mtDNA disorders.