Mitochondrial Diseases and Genetics

Flashcards covering key concepts related to mitochondrial diseases, their genetics, functions, and implications for human health.

What are mitochondrial diseases?

A group of disorders that arise from dysfunction of the mitochondrial respiratory chain.

What are the two genomes involved in mitochondrial gene mutations?

Nuclear DNA (nDNA) and Mitochondrial DNA (mtDNA).

What is the origin of mitochondria?

Endosymbiotic origin; acquired by an eucaryotic host cell more than 2 billion years ago.

At what age can mitochondrial diseases onset occur?

Any age.

What does the fission/fusion machinery of mitochondria do?

It helps generate young mitochondria and eliminate old, damaged ones.

List one function of mitochondria.

ATP energy production through oxidative phosphorylation (OXPHOS).

How many mitochondrial DNA (mtDNA) genes are there?

37 mitochondrial DNA genes.

What is heteroplasmy?

The presence of different mitochondrial genomes in the same cell or tissue.

What do maternal inheritance and paternal inheritance refer to in mitochondrial genetics?

Maternal inheritance means mtDNA is inherited from the mother, while paternal inheritance is rare and occurs in some species.

What is the genetic bottleneck in the context of heteroplasmy?

A situation where each oocyte can inherit different proportions of mutated mtDNA.

What can trigger increased risk of developing disorders in individuals with specific mtDNA mutations?

Environmental factors such as smoking or alcohol consumption.

What does the concept of threshold effect mean in mitochondrial disorders?

A level of mutated molecules must be reached before they affect ATP production.

Which mitochondrial disease is associated with single base pair variants?

MELAS and MERRF.

What role do haplogroups play in mitochondrial health?

They can modulate the clinical expression of disorders and influence disease risk.

What is mitochondrial oxidative phosphorylation (OXPHOS)?

A process by which mitochondria produce ATP as energy.

How are mtDNA mutations passed to offspring?

Primarily through maternal inheritance from the oocyte.

What phenomenon can result in different clinical outcomes in offspring?

Genetic bottleneck due to varying proportions of mtDNA mutations inherited.

What has been associated with the m.1555A>G variant in mtDNA?

Increased risk of sensorineural deafness when exposed to aminoglycoside antibiotics.

What is the mutation rate of mtDNA compared to nuclear DNA?

Mitochondrial DNA has a higher mutation rate due to less effective repair mechanisms.

What are the two types of mtDNA mutations mentioned in the lecture?

Single base pair variants and mtDNA rearrangements.

What is the significance of the displacement loop (D-loop)?

It contains regulatory sequences for transcription and replication of mtDNA.

How does heteroplasmy change over an individual's life?

Different tissues can have varying levels of heteroplasmy at different times.

What link has been suggested between mitochondrial haplogroups and late-onset diseases?

Certain haplogroups are associated with increased risks of diseases like Parkinson’s and Alzheimer’s.

What happens to sperm mitochondria after fertilization?

They are tagged with ubiquitin and destroyed by autophagy.

What unique feature characterizes the organization of mtDNA?

Fewer genes organized in a polycistronic sequence.

What are NUMTs?

Nuclear-encoded mitochondrial sequences resulting from DNA transfer from mitochondria to the nucleus.

What are the implications of heteroplasmic pathogenic mtDNA mutations?

They often show a threshold effect where a high proportion is needed to affect ATP production.

What is the importance of the cristae structure in mitochondria?

It increases the surface area for oxidative phosphorylation.

What is a key factor that contributes to the symptoms of mitochondrial disorders?

The degree of heteroplasmy and the mtDNA mutation load.