MITO DISEASE
Source: BusinessStandard
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Context
- Scientists are currently preparing for a clinical trial to determine whether mitochondrial donation is safe and effective, following the passage of a law in Australia in 2022 that will allow for the practice.
Details
Mitochondrial Donation
- An IVF-based procedure that prevents the transmission of faulty mitochondrial DNA, allowing families to have healthy, genetically related children.
- Process:
- Hormone Injections: Stimulate egg production in both the donor and the affected individual.
- Egg Retrieval: Collect eggs from both the donor and the affected individual using an ultrasound-guided procedure.
- Nuclear DNA Transfer: Extract the nuclear DNA from the affected individual’s egg and insert it into the donor egg with healthy mitochondria.
- Fertilization: Use sperm from the intending father to fertilize the modified donor egg​​.
Legal and Ethical Considerations
- Maeve's Law: The Mitochondrial Donation Law Reform Bill 2021, passed by the Australian Senate in 2022, allows mitochondrial donation for research and clinical trials under strict regulations.
- Requirements:
- Facilities must obtain special permits.
- Initial licenses for pre-clinical and clinical trial research to ensure safety and effectiveness​​.
What is Mitochondrial Disease?
- Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria, the organelles that generate energy for the cell.
- These diseases can affect multiple organs and systems, including the brain, heart, liver, muscles, kidneys, and endocrine system.
- Affects 1 in every 5,000 people, making it a common inherited metabolic condition.
Causes
- Mitochondrial diseases are primarily genetic, resulting from mutations in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA).
- They can be inherited in several ways:
- Autosomal Recessive/Dominant Inheritance: Mutations in nDNA inherited from both or one parent.
- Mitochondrial Inheritance: Mutations in mtDNA passed down from the mother.
- De Novo Mutations: New mutations that occur spontaneously without a family history​​.
Symptoms
Symptoms of mitochondrial diseases vary widely and can include:
- Muscle weakness and exercise intolerance
- Neurological issues such as seizures, migraines, and developmental delays
- Cardiomyopathy and other heart issues
- Liver and kidney dysfunction
- Endocrine problems, including diabetes and growth delays
- Gastrointestinal disturbances
- Visual and hearing impairments​​.
Types of Mitochondrial Diseases
There are several types of mitochondrial diseases, each with unique characteristics. Some notable types include:
- Leigh Syndrome: Severe neurological disorder
- MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes)
- MERRF (Myoclonic Epilepsy with Ragged Red Fibers)
- Kearns-Sayre Syndrome
- Barth Syndrome
- Alpers Disease
- Chronic Progressive External Ophthalmoplegia (CPEO)
- Friedreich's Ataxia​
Mitochondria
- Mitochondria are double-membrane-bound organelles found in the cytoplasm of almost all eukaryotic cells.
- They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy.
Structure of Mitochondria
- Outer Membrane
- Smooth and permeable to small molecules and ions.
- Contains proteins called porins that allow molecules to pass through.
- Involved in various functions such as lipid metabolism and the maintenance of mitochondrial shape.
- Intermembrane Space
- The area between the inner and outer membranes.
- Contains enzymes that use the ATP moving out of the matrix to phosphorylate other nucleotides.
- Plays a role in apoptosis (programmed cell death).
- Inner Membrane
- Folded into structures called cristae to increase surface area.
- Contains proteins involved in the electron transport chain and ATP synthesis.
- Impermeable to most ions and molecules; transport is highly regulated.
- Matrix
- Enclosed by the inner membrane.
- Contains mitochondrial DNA (mtDNA), ribosomes, and enzymes involved in the citric acid cycle (Krebs cycle) and fatty acid oxidation.
- The site of ATP production through oxidative phosphorylation.
Functions of Mitochondria
- Energy Production
- Primary site of ATP production via oxidative phosphorylation.
- Citric acid cycle (Krebs cycle) takes place in the matrix, generating high-energy electron carriers.
- Regulation of Metabolic Activity
- Involved in various metabolic tasks including the synthesis of certain steroids and heme.
- Plays a role in the regulation of cellular metabolism.
- Apoptosis: Mitochondria release cytochrome c, triggering the cascade of events leading to programmed cell death.
- Calcium Storage: Store calcium ions and help maintain cellular calcium homeostasis.
- Heat Production: In brown adipose tissue, mitochondria generate heat through a process called non-shivering thermogenesis.
- ROS Production: By-products of the electron transport chain include reactive oxygen species (ROS), which play roles in cell signaling and homeostasis.
Mitochondrial DNA
- mtDNAis circular and maternally inherited.
- Encodes 37 genes, including 13 for proteins, 22 for tRNA, and 2 for rRNA.
- Mutations in mtDNA can lead to various mitochondrial diseases.
Biogenesis and Dynamics Biogenesis
Dynamics
|
Summary of all major cell organelles
Organelle |
Structure |
Function |
Presence |
Nucleus |
Double membrane with pores; contains nucleolus and chromatin |
Stores genetic material (DNA); controls cellular activities; site of transcription |
Eukaryotic cells |
Mitochondria |
Double membrane; inner membrane folded into cristae |
ATP production through oxidative phosphorylation; regulates cellular metabolism |
Eukaryotic cells |
Ribosomes |
Composed of rRNA and proteins; can be free or bound |
Protein synthesis |
All cells |
Endoplasmic Reticulum (ER) |
Network of membranous tubules; rough ER has ribosomes, smooth ER does not |
Rough ER: Protein synthesis and processing; Smooth ER: Lipid synthesis and detoxification |
Eukaryotic cells |
Golgi Apparatus |
Stacks of flattened membranous sacs |
Modifies, sorts, and packages proteins and lipids for secretion or delivery to other organelles |
Eukaryotic cells |
Lysosomes |
Membrane-bound vesicles containing hydrolytic enzymes |
Breakdown of macromolecules; recycling of cellular components; apoptosis |
Animal cells primarily |
Peroxisomes |
Membrane-bound vesicles containing oxidative enzymes |
Breakdown of fatty acids; detoxification of harmful substances |
Eukaryotic cells |
Chloroplasts |
Double membrane with internal thylakoid stacks |
Photosynthesis; conversion of light energy into chemical energy (glucose) |
Plant cells and algae |
Vacuoles |
Membrane-bound sacs; large central vacuole in plant cells |
Storage of nutrients and waste products; maintenance of turgor pressure in plant cells |
Eukaryotic cells |
Cell Membrane |
Phospholipid bilayer with embedded proteins |
Selective barrier; regulates transport of substances in and out of the cell |
All cells |
Cell Wall |
Rigid structure outside the cell membrane; composed of cellulose in plants |
Provides structural support and protection |
Plant cells, fungi, some prokaryotes |
Cytoskeleton |
Network of protein fibers (microfilaments, intermediate filaments, microtubules) |
Maintains cell shape; facilitates cell movement and division; transports materials within the cell |
Eukaryotic cells |
Centrioles |
Cylindrical structures composed of microtubules |
Involved in cell division; organizes the mitotic spindle |
Animal cells primarily |
Nucleolus |
Dense region within the nucleus |
Ribosome biogenesis |
Eukaryotic cells |
Cytoplasm |
Gel-like substance within the cell membrane |
Holds organelles; site of many metabolic pathways |
All cells |
Plastids |
Double membrane; includes chloroplasts, chromoplasts, and leucoplasts |
Involved in synthesis and storage of food |
Plant cells |
Cilia and Flagella |
Hair-like structures on cell surface |
Movement of the cell or movement of fluids over the cell surface |
Some eukaryotic cells |
Sources:
PRACTICE QUESTION Q: Consider the following statements regarding Mitochondrial DNA (mtDNA):
Which of the statements given above is/are correct? a) 1 and 2 only Answer: d) |