Curriculum
Module 07 · 70 min
Bioenergetics & Mitochondrial Cell Biology
Membrane potential, ROS, mitophagy, and the inheritance of mitochondrial disease.
CoreClinicalResearch
Topics
What this module covers
- 01Electron transport chain and chemiosmosis (Mitchell)
- 02ATP synthase rotation; F1Fo mechanism
- 03Reactive oxygen species: source, signalling, and damage
- 04Mitochondrial dynamics: fission (Drp1) / fusion (Mfn1/2, OPA1)
- 05Mitophagy: PINK1/Parkin, BNIP3, FUNDC1
- 06Mitochondrial DNA, heteroplasmy, maternal inheritance, mtDNA replacement therapy
Deep dives
Lesson sub-pages
Learning objectives
By the end of this module you will be able to
- L01Predict, given a Complex inhibitor, the metabolic and redox consequences in a tissue.
- L02Explain heteroplasmy, threshold effect, and tissue-specific phenotypes in mtDNA disease.
- L03Distinguish damaging vs signalling roles of ROS.
Expected takeaways
What you should walk away believing
- →Most ATP comes from the proton gradient, not substrate-level phosphorylation.
- →ROS is signal at low levels and damage at high — antioxidant supplementation has not improved outcomes in most settings.
- →Mitochondrial diseases are characterised by tissue thresholds, not all-or-nothing inheritance.
Core summary
At the Core level
The mitochondrion is not just 'the powerhouse' — it is a signalling hub for apoptosis (cytochrome c release), innate immunity (mtDNA as DAMP via cGAS-STING), and metabolism. Its inner-membrane proton gradient drives ATP synthesis, ion transport, and protein import.
Myth vs reality
Common misconception
Claim
Antioxidant supplements prevent disease.
Reality
Large RCTs of vitamin E, β-carotene, and vitamin C have generally shown no benefit; β-carotene increases lung-cancer risk in smokers (CARET, ATBC).
Evidence-graded claims
Claims, scored A–F
A
ATP synthase is a rotary molecular machine
Direct visualisation by Yoshida & Walker (Nobel 1997).
B
Mitochondrial donation prevents transmission of severe mtDNA disease
Approved in UK; case-by-case authorisation; outcomes still being collected.
D
NMN supplementation extends human healthspan
Strong rodent data; human RCTs are small and mixed.
Quiz
Check your understanding
Q1. Heteroplasmy means:
Q2. Complex IV is inhibited by:
Flashcards
Lock it in
1 / 3
Front
Mitchell's chemiosmotic hypothesis?
Click to flip
Suggested reading
Primary literature
- Mitochondria as signaling organelles — Chandel, BMC Biology 2014 ↗
- Mitochondrial replacement techniques — HFEA UK guidance ↗