Peroxisomes and Mitochondria Flashcards
What are Peroxisomes?
Small single membrane organelles found in all cells
Peroxisomal Proteins are all nuclear encoded
What metabolic reactions do peroxisomes carry out?
Oxidative reactions using molecular oxygen
E.g. breakdown normal metabolites and harmful compounds
Synthesis of bile acids and plasmalogens
What is Catalase?
Enzyme in peroxisomes that removes excess H2O2
What are the two mechanisms of peroxisome formation?
Vesicles budding from the ER and fuse
Growth and division of existing peroxisomes (more rapid)
These two mechanisms allow response to different metabolic needs
Where are peroxisome matrix proteins synthesized?
Free ribosomes and imported as folded polypeptides
What is Peroxisomal targeting sequence 1?
Ser-Lys-Leu
Labels peroxins for import via ER pathway
What recognizes the PTS1 signal and what is the next step?
Pex5 receptor
Pex5/Cargo complex binds to a docking complex on the peroxisome
What is mPTS?
Targeting signal on peroxins that is recognized by Pex19
How are oxidized flavins regenerated in peroxisomes?
Regenerated with oxygen in a reaction that produces hydrogen peroxide
Why do 2-carbon units oxidized in the peroxisomes produce fewer ATPs?
Enzyme transfers liberated electrons directly to oxygen instead of the electron transport chain
What is FAD-dependent acyl-CoA oxidase?
Catalyzes the initial double bond formation in peroxisomal B-oxidation
Inactive with carbon chains of 8 or fewer
Short-chain products must be transferred to mitochondria to be broken down
Where are plasmologens made?
Peroxisomes
Protective versus oxidant stress
What are the recessive genetic disorders associated with Peroxin mutations?
Rhizomelic Chondrodysplasia punctata type 1 (RCDP type 1)
Zellweger spectrum disorders
Describe Zellwegger Spectrum Disorders.
Disrupted peroxisome assembly
Peroxisomes absent in hepatocytes and fibroblasts
Accumulation of VLCFA, phytanic acid, plasmologen deficiency
What are the symptoms of Zellwegger Syndrome?
Craniofacial, neurologic, and ocular abnormalities
Impaired neuronal migration and severe demyelination
What is Neonatal Adrenoleukodystrophy (NALD)?
Milder form of ZS
Patients have milder ZS symptoms with adrenal atrophy
What is Infantile Refsum’s Disease?
No neonatal abnormalities and only mild dysmorphia
Mental retardation, retinitis pigmentosa, neurosensory deafness, growth retardation
Describe mitochondrial fusion and fission.
Happens dynamically
Fusion allows exchange of genetic material
Fission is important in distribution of mitochondria between daughter cells at cell division
What four processes does the mitochondria carry out?
Oxidation of nutrients in TCA cycle
Energy generation - Oxphos
Integrator of cellular death signals - apoptosis
Transcription/Translation
Where does mitochondrial protein import occur?
Regions where the outer and the inner membranes are close together
How many different types of signal sequences are there for mitchondrial protein import and what is their general structure?
4
Predominantly positive AA’s, often in an alpha helix
What is responsible for making the mitochondrial outer membrane fairly permeable?
Porins or voltage dependent anion channel
What is the role of Hsp70?
Maintain protein in a semi-folded state in the cytosol
What is the function of TOM complex?
Mediates protein transport across the outer membrane
What is the function of TIM23 complex?
Mediates protein transport across the inner membrane into the matrix
What is the function of matrix processing peptidase?
Cleaves the targeting pre-sequence within the matrix
What is the function of Mim1?
Responsible for inserting proteins into the outer membrane with a single transmembrane domain
How do B-barrel proteins get inserted into the outer membrane?
Pass through TOM
Bound by Tim9-Tim10 and carried to SAM
SAM mediates their insertion into the outer membrane
How are proteins with multiple transmembrane domains that have an internal import signal transported?
After transport through TOM, tim9-10 bring them to Tim22
Tim22 then facilitates transfer into the inner membrane
What is the function of Oxa1?
Responsible for mediating the insertion of inner membrane proteins that are transcribed in the mitochondria
What is Human Deafness Dystonia Syndrome?
X-linked neurodegenerative disorder
Defect in Tim8
What are the symptoms of Human Deafness Dystonia Syndrome?
Postlingual progressive sensorineural deafness
Dystonia
Spasticity, Dysphagia
Mental deterioration
Cortical blindness
What is cardiolipin?
Lipid that contains four fatty acyl chain and is found almost exclusively in the inner mitochondrial membrane
Essential for the optimal function of numerous enzymes
What is Barth Syndrome?
Infantile cardiomyopathy linked to the X-chromosome
Associated with decrease in tetralinoleoyl species of cardiolipin and accumulation of monolysocardiolipin
Metabolic defect involves phospholipid acyltransferase
What are the symptoms of Barth Syndrome?
Cardiomyopathy
Skeletal myopathy
Neutropenia
Growth retardation
