Top Banner
Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: [email protected]
24

Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: [email protected].

Jan 19, 2016

Download

Documents

Jabari Tagge
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Mitochondria

Guest lecturer: Chris Moyes, Dept of BiologyContact: [email protected]

Page 2: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Endosymbiosis

Mitochondria formed as a result of an endosymbiotic event around 2 billion years ago.

Page 3: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

From: Gerhart and Kirschner: Cells, Embryos and Evolution

Page 4: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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

Page 5: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Mitochondrial compartments

Page 6: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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

• Dynamin-Related Protein causes fission

• Fuzzy Onion Protein (FZO) causes fusion

Page 7: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Mitochondrial reticulum

Page 8: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Fusion and fission proteins regulate network

Page 9: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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

Page 10: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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

Page 11: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Show 14-10, gen overview

Overview of energy production by OXPHOS

Page 12: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Reducing equivalents are produced in the oxidation of carbohydrate

and lipid

Page 13: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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)

Page 14: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Proton motive force (PMF)

The PMF is an electrochemical gradient of membrane potential (ΔΨ) and pH (ΔpH)

Page 15: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

The PMF supplies the energy for active transport into the mitochondria

Page 16: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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)

Page 17: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Oxidation and phosphorylation are coupled by a shared dependence on the PMF

Page 18: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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?

Page 19: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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 “over-charging”, thereby reducing ROS production.

Page 20: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Mitochondrial biogenesis requires proteins encoded in 2 genomes (nucleus and mtDNA)

Nucleus

•encode most proteins

•2 copies of each gene per diploid cell

•genes regulated independently

•proteins imported by post-translational import from cytoplasm

mtDNA

•encodes few proteins

•1000’s of copies per cell

•genes transcribed as a polycistron

•transcribed and translated directly in mitochondria)

Page 21: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

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

Page 22: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Editing of mtDNA polycistron

Page 23: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Nuclear gene expression is coordinated by transcription

factor networks

Page 24: Mitochondria Guest lecturer: Chris Moyes, Dept of Biology Contact: moyesc@biology.queensu.ca.

Mt enzyme synthesis requires coordinated gene expression and

accessory factors