2009 Lecture 7
Contents
- 1 Cell Energy Production - Mitochondria
- 2 Introduction
- 3 Objectives
- 4 Double Membrane Organelles
- 5 History Mitochodria
- 6 Evolution Mitochondria
- 7 Chloroplasts
- 8 Mitochondria
- 9 Mitochondrial Division and Fusion
- 10 Energy Production
- 11 Apoptosis
- 12 Abnormalities
- 13 References
- 14 Mitochondrion Images
- 15 2009 Course Content
Cell Energy Production - Mitochondria
Introduction
This lecture introduces the cytoplasmic organelles that produce the energy required for cellular processes to occur. In recent years mitochondria have also been shown to have important roles in other cellular functions, in particular, cell death by apoptosis. This second role will be covered in detail in later lectures in this current series.
Dr Mark Hill (2009)
Lecture Audio
The University has a system for automated recording of lectures called Lectopia. Lectopia requires login using your student number and unipass. I will be adding the link to each iLecture Audio following the Lecture. Due to the automated recording method, most lectures begin 4-5 minutes into MP3 recordings and occasionally stop before the lecture does. 2009 All Audio Files
- Lecture 7: Cell Energy Production - Mitochondria Lecture Date: 31-03-2009 Lecture Time: 13:00 Venue: BioMed F Speaker: Mark Hill
Archive
(MH - note that content will not match exactly current lecture structure but has been selected as having similar content)
- 2008 Online Lecture 2008 Online content
- 2007 Lecture Slides PDF 1 slide/page (view only, 53 pages, 1 Mb) | 6 slides/page (print, 9 pages, 516 Kb) | outline (print no images, 6 pages, 92 Kb)
Objectives
- Broad understanding of processes requiring energy within the cell
- Brief understanding structure and function of plant chloroplast
- Understand the structure and function of plant and animal mitochondria
- Brief understanding of mitochondria evolution
- Brief understanding of mitochondrial abnormalities
Double Membrane Organelles
- Nucleus - all eukaryotes
- Chloroplasts - plants
- Mitochondria - plants and animals
History Mitochodria
1857 Kölliker discovers mitochondria in muscle
1929 Karl Lohmann discovered ATP
1940s and 1950s ATP is formed in cell respiration in mitochondria and photosynthesis in chloroplasts of plants
1960 Efraim Racker and co-workers isolated, from mitochondria, the enzyme "F o F 1 ATPase" now call ATP synthase
1963 There’s DNA in those organelles DNA is directly visualized in first chloroplasts and then mitochondria, from the JCB Archive.
1992 Wallace identified degenerative disease caused by mtDNA mutations
1997 Nobel Prize in Chemistry - The three laureates have performed pioneering work on enzymes that participate in the conversion of the "high-energy" compound adenosine triphosphate (ATP).
- Paul D. Boyer and John E. Walker "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)"
- Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase
Evolution Mitochondria
- primitive Eubacterium
- symbiotic relationship with eukaryotic cell
- circular DNA
- see antibiotic-induced deafness due to similarity of mitochondrial and bacterial ribosomes
- genes transferred to nucleus
- mitochondrial genome bp
- 366,924 Arabidopsis
- 16,569 Human
- 5966 Plasmodium
Chloroplasts
- Double membrane cytoplasmic organelle
- present in photosynthetic Eubacteria, algae and plants
- thought to originate as an endosymbiotic cyanobacteria (blue-green algae)
Function
- photosynthesis
- chlorophyll captures light energy
- chloroplasts interact with peroxisomes
Structure
- flat discs usually 2 to 10 micrometer in diameter and 1 micrometer thick. In
- plants 5 μm in diameter and 2.3 μm thick
- inner and an outer phospholipid membrane
- intermembranous space
- stroma
- stacks of thylakoids (site of photosynthesis)
- contains copies of small circular DNA
- ribosomes
- proteins transported to the chloroplast
(MH - will not cover this cell organelle in any depth in current course)
Mitochondria
- Greek, mito = thread; chondrion = granule
- Located throughout cytoplasmic compartment
- has itself several membrane enclosed compartments
- each compartment has different function
- Ancient aerobic organisms in symbiosis (endosymbiosis)
present in all cells
Mitochondria Function
- Energy production
- Respiratory Chain
- Apoptosis role
- Programmed cell death
Mitochondria Structure
- Double membrane
- outer membrane
- intermembrane space
- inner membrane
- crista (plural, cristae)
- originally considered specialized folds of the inner membrane
- variable invaginations with narrow tubular connections to each other and by crista junctions to the peripheral region of inner membrane
- matrix
Mitochondria Shape
- Come in different shapes & sizes
- Can rapidly change shape (minutes)
EM: Mitochondria EM: Mitochondria EM: Mitochondria Mitochondrial Morphology
Mitochondria Location
- cells with high energy requirements: Muscle, sperm tail, flagella
- generally located where energy consumption is highest in the cell
- Mitochondria (fibroblasts)
- Mitochondria (sperm)
- Packed around initial segment
- Energy for sperm motility, microtubules (9+2)
Mitochondria Components
Outer Membrane
- porin - membrane channel, allows ions amd metabolites into the mitochondria
Intermembrane Space
- enzymes that use ATP
Inner Membrane
- cardiolipin - phospholipid
Cristae
- Adenosine triphosphate (ATP) synthase
- respiratory electron transfer chain proteins
- transport proteins
Matrix
- metabolic enzymes of citric acid cycle (=Krebs) (100s of enzymes) (MH- do not need to know biochemical details of this cycle)
- genetic material DNA, tRNA, ribosomes
Mitochondria DNA
- double stranded circular DNA (mitoDNA. mtDNA)
- 1981 complete human sequence (16,569 nucleotides)
- 37 genes
- encodes 13 polypeptides involved in oxidative phosphorylation
- remaining genes transfer RNA (tRNA) and ribosomal RNA (rRNA)
- multiple copies within the matrix
- maternally inherited
- remainder encoded by nuclear DNA
- proteins made in cytosol and imported into mitochondria
Links: Home Reference - Mitochondrial DNA
Mitochondria Protein Synthesis
- yeast - Petite mutants
- all mitochondrion-encoded gene products missing
- forms small anaerobic colonies
- organelle is constructed entirely from nucleus-encoded proteins
Many mitochondrial proteins are encoded by nuclear DNA
- synthesis begins in the cell cytoplasm
- imported into the mitochondria
- targeting similar to signal sequence for RER
- once in matrix signal sequence is cleaved (by Hsp70)
- protein then folds (by Hsp60)
- proteins for mitochondrial membrane or intermembranous space
- have additional signal following matrix localization
Links: Replication and preferential inheritance of hypersuppressive petite mitochondrial DNA | Home Reference - Mitochondrial DNA
Mitochondrial Division and Fusion
Mitochondria Fission
- Mitochondrial Division
- Divide independently of the whole cell cycle
- Generated by existing mitochondria
- inward furrowing like bacterial division
- mitochondria lack FtsZ ring (seen in bacteria)
- rely on dynamin on the cytosolic face for fission
Mitochondrial inheritance
Mitochondrial Fusion
- when two separate mitochondria join as one
- fission and fusion considered to be balanced
- disruption causes normal tubular network of mitochondria to fragment into short rods or spheres
- Requires large GTPases
- Mitofusins 1 and 2 (Mfn1, Mfn2) and OPA1
Energy Production
Respiration
- Raw Materials
- Oxygen
- Pyruvate & Fatty Acids
- Products
- Carbon Dioxide
- Adenosine Triphosphate (ATP)
Apoptosis
Mitochondria in addition to energy production, have a second major function related to programmed cell death by apoptosis.
- cytochrome C release activates caspases
- other changes include
- electron transport, loss of mitochondrial transmembrane potential
- altered cellular oxidation-reduction
- Bcl-2 family proteins (pro- and antiapoptotic)
- Vesicular Mitochondria
- begin to appear during the release of cytochrome C which initiates mitochondrial mediated apoptosis
- transformation from normal morphology
- with an inner boundary membrane connected to lamellar cristae via crista junctions
- multiple vesicular matrix compartments
- facilitates membrane fission or fragmentation as the matrix is fragmented at this stage
- fragmentation of the mitochondrion requires only outer membrane fission
(MH- this topic will be covered again in the Cell Death Lecture)
Links: Lecture - Cell Death 1 | Lecture - Cell Death 2 | Movie - Vesicular Mitochondria | Role of mitochondria in apoptosis
Abnormalities
Mitochondrial Myopathies
- A group of several diseases
- Kearns-Sayre syndrome (KSS) Genes and Disease - Kearns-Sayre syndrome
- Leigh's syndrome Genes and Disease - Leigh's syndrome
- mitochondrial DNA depletion syndrome (MDS)
- mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) Genes and Disease - MELAS
- myoclonus epilepsy with ragged red fibers (MERRF)
- mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
- neuropathy, ataxia and retinitis pigmentosa (NARP) Genes and Disease - NARP
- Pearson syndrome Genes and Disease - Pearson syndrome
- Progressive external ophthalmoplegia (PEO) Genes and Disease - Progressive External Ophthalmoplegia
Friedreich's ataxia (FRDA)
- mutation in gene for frataxin (a mitochondrial iron (Fe) chaperone)
- mechanism may be a mitochondrial iron (Fe) loading and reactive oxygen species
- animal models show H2O2 is an important pathogenic substrate underlying the phenotypes arising from frataxin deficiency
- Genes and Diseases - Friedreich's ataxia
Charcot–Marie–Tooth type 2A
- inherited neuropathy
- caused by mutations in mitofusin 2
- proper regulation of mitochondrial dynamics required in neurons
Leber Hereditary Optic Neuropathy
- maternally inherited cause of blindness Genes and Diseases - LHOM
- mutation of mitochondrial DNA (mtDNA)
- three common mtDNA mutations: G11778A, T14484C, G3460A
Aminoglycoside-induced deafness
- due to aminoglycoside antibiotic treatment Genes and Diseases - Aminoglycoside-induced deafness
- gentamycin, streptomycin, and tobramcyin
- similarity of mitochondrial ribosomes to bacterial ribosomes
Other
- Cyclic vomiting syndrome?
Links: Genes and Diseases -Mitochondria and Disease | GeneReviews - Mitochondrial Disorders Overview | Genes and Diseases - Friedreich's ataxia | Muscular Dystrophy Association - Mitochondrial Myopathies | The Cleveland Clinic - Mitochondrial Myopathies | Genes and Diseases | OMIM - Online Mendelian Inheritance in Man
References
Textbooks
Essential Cell Biology
- Chapter 13 Energy Generation in Mitochondria and Chloroplasts
- Chapter 14 Intracellular Compartments and Transport
Molecular Biology of the Cell
Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002
Molecular Cell Biology
Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999
- Mitochondria Are the Principal Sites of ATP Production in Aerobic Cells
- Figure 16-7. A three-dimensional diagram of a mitochondrion cut longitudinally
The Cell- A Molecular Approach
Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000
- The Cell - A Molecular Approach - III. Cell Structure and Function 10. Bioenergetics and Metabolism - Mitochondria, Chloroplasts, and Peroxisomes
- Mitochondria
Search Online Textbooks
- "mitochondria" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
- "chloroplast" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
Books
PubMed
- PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
- PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
- Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
- Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez
Search Pubmed
- "mitochondria" PubMed reviews | PubMed all articles | PMC reviews | PMC all articles | OMIM | Entrez all databases
Reviews
- Mitochondrial fragmentation in neurodegeneration. Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E. Nat Rev Neurosci. 2008 Jul;9(7):505-18. Review. PMID: 18568013
- Emerging functions of mammalian mitochondrial fusion and fission. Chen H, Chan DC. Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R283-9. Review. PMID: 16244327
Articles
- Bcl-x L increases mitochondrial fission, fusion, and biomass in neurons. Berman SB, Chen YB, Qi B, McCaffery JM, Rucker EB 3rd, Goebbels S, Nave KA, Arnold BA, Jonas EA, Pineda FJ, Hardwick JM. J Cell Biol. 2009 Mar 9;184(5):707-19. Epub 2009 Mar 2. PMID: 19255249
Mitochondrion Images
For a full selection of see Cell Biology Images - Mitochondria Images
2009 Course Content
Lectures
Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cell Mitochondria | Cell Junctions | Cytoskeleton Introduction | Cytoskeleton 1 Intermediate Filaments | Cytoskeleton 2 Microtubules | Cytoskeleton 3 Microfilaments | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells | Stem Cells | Development | Revision
Laboratories
Introduction to Lab | Microscopy Methods | Preparation/Fixation | Immunochemistry | Cell Knockout Methods | Cytoskeleton Exercise | Confocal Microscopy | Tissue Culture 1 | Tissue Culture 2 | Microarray Lab visit
Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G