Transcript Mitochondria

Mitochondria
Guest lecturer: Chris Moyes, Dept of Biology
Contact: [email protected]
Endosymbiosis
Mitochondria formed as a
result of an endosymbiotic
event around 2 billion years
ago.
From: Gerhart and Kirschner: Cells, Embryos and Evolution
Mitochondrial compartments
Inner membrane
•Respiratory chain and ATP synthase
•impermeable to most charged molecules
•highly folded into invaginations called cristae.
Outer membrane
•Permeable to larger molecules
Matrix
•Enzymes of the citric acid cycle, mtDNA
Intermembrane space
•space between inner and outer membranes
Mitochondrial compartments
Mitochondrial morphology and movement
Mitochondria are dynamic organelles
•they may exist as individual organelles
•may become elaborate network
•move throughout the cell on cytoskeleton
Changes in the network are mediated by fission and
fusion proteins
• Fuzzy Onion Protein (FZO) causes fusion
• Dynamin-Related Protein causes fission
Mitochondrial reticulum
Fusion and fission proteins regulate network
Mitochondrial energy production
Three major steps in oxidative phosphorylation
1) Production of reducing equivalents (NADH,
FADH2) from glycolysis, fatty acid oxidation, and
the citric acid cycle
2) Electron transport and generation of proton
motive force
3) Phosphorylation - Synthesis of ATP, driven by
the proton motive force
Mitochondria make other products
Mitochondria produce biosynthetic precursors
OXPHOS also leads to the production of:
•Superoxide: formed when O2 steals
electrons from the ETC complexes
•Heat: a by-product of the reactions of
OXPHOS
Overview of energy production by OXPHOS
Show 14-10, gen overview
Reducing equivalents are produced in the
oxidation of carbohydrate and lipid
Oxidation and Electron Transport
Electrons from NADH and FADH2 are passed down
respiratory chain to O2
Electron transport expels protons, creating a proton
gradient- the proton motive force (PMF)
Proton motive force (PMF)
The PMF is an electrochemical gradient of membrane
potential (ΔΨ) and pH (ΔpH)
The PMF supplies the energy for active
transport into the mitochondria
Phosphorylation
The F1Fo ATPase (or
ATP synthase) is a
molecular motor
-it uses the PMF to
make ATP
-it can also be reversed
(using ATP hydrolysis
to recharge the PMF)
Oxidation and phosphorylation are coupled
by a shared dependence on the PMF
Because of this “coupling”, the two
processes are interdependent
•If the PMF is large, what would you predict about
oxygen consumption?
•If you took away oxygen, what would happen to the
PMF?
•What would an increase in [ADP] do to the oxygen
consumption?
•What would happen to ATP synthesis and oxygen
consumption if the inner membrane became leaky?
Uncoupling proteins
Many mammals warm vital tissues using brown fat
Adipose tissue with abundant mitochondria that
possess a the protein thermogenin (or uncoupling
protein 1).
UCP-1 short-circuits the proton gradient,
increasing VO2 and heat production.
All eukaryotes have proteins related to UCPs, that
are thought to prevent the PMF from “overcharging”, thereby reducing ROS production.
Mitochondrial biogenesis requires proteins
encoded in 2 genomes (nucleus and mtDNA)
mtDNA
Nucleus
•encodes few proteins
•encode most proteins
•1000’s of copies per cell
•2 copies of each gene
per diploid cell
•genes transcribed as a
polycistron
•transcribed and
translated directly in
mitochondria)
•genes regulated
independently
•proteins imported by
post-translational import
from cytoplasm
Peculiarities of mtDNA
mtDNA is a very compact genome
-genes attached end to end, with mRNA regions
interspersed among rRNA and tRNA genes
-tRNA excision liberates protein-coding genes
-many genes lack a full termination codon (TAA)
Diversity
-maternal origin (most animals)
-many cells have multiple genotypes within a
single cell (heteroplasmy)
-defects accumulate with age
Editing of mtDNA polycistron
Nuclear gene expression is coordinated
by transcription factor networks
Mt enzyme synthesis requires coordinated
gene expression and accessory factors