Lecture 11 - Organelles 1 Flashcards Preview

Unit 1 - Molecular and Cellular Principles of Medicine > Lecture 11 - Organelles 1 > Flashcards

Flashcards in Lecture 11 - Organelles 1 Deck (15):

Proteins are imported into organelles by what 3 mechanisms?

1. Transport via nuclear pores - selective gates which actively transport proteins in both directions

2. Transport via protein translocators - protein translocators within organelle membrane directly transport proteins from cytosol into organelle. Occurs co-transitionally for the ER and post-translationally for the mitochondira and peroxisomes.

3. Transport via vesicles - vesicles containg proteins from lumen and membrane of one organelle pinch off and then fuse with the membrane of a second orgnaelle (ex. ER to Golgi, golgi to plasma membrane)


How does a cell know where to deliver each newly synthesized protein?

Signal sequences/sorting signals - used to direct proteins to correct organelle, 3-60 amino acid stretch in protein, may be removed by a signal peptidase


Describe mitochondria's structure and function.

Function: Power plants of the cell - 90% of the energy


Structure: Outer membrane - separates mitochondrian from cytosol, has porins (channels for small molecules)

Inner membrane - encloses matrix space, convoluted (cristae), contains proteins for e- transport chain and ATP synthase, transport proteins, electrochemical gradient maintained across it

Intermembrane space - small space located between inner and outer membranes, contains cytochrome C, component of e- transport chain

Matrix space - high concentration of enzymes including those that break down fatty acids and those in the citric acid cycle, location of mitochondrial DNA genome 


Briefly describe the conversion of fatty acids and pyruvate to ATP

A image thumb

Describe the role of mitochondria in Apoptosis

The release of cytochrome C from the intermembrane space into the cytosol triggers activation of the caspase cascade, an intracellular proteolytic cascade responsible for cleaving key cellular proteins


Describe the transport of proteins into mitochondria

Proteins destined for mitochondria are typically synthesized with an N-terminal signal sequence and transported post-translationally. Transport is mediated by two protein translocators - TOM and TIM.


Precursor protein binds to a receptor associated with TOM (transporter in outer membrane). TOM/receptor complex diffuse laterally until it encounters a TIM (transporter in inner mem). 


Precursor protein is translocated across both membranes, signal sequence first - chaperone proteins help pull the protein. Signal sequence is cleaved off by mitochondiral signal peptidase and protein folds into final confirmation.


Describe the mitochondrial genome

Very small circular double stranded DNA

Encodes 2 rRNAs, 22 tRNAs, 13 mRNAs

Little regulatory sequence

No introns

Genetic code is slightly different (tRNAs don't carry same proteins)

~10-20 copies per mitochondrion

Makes some of the components for the e- transport chain


Describe the replication of Human Mitochondrial DNA

Mitochondria carry out their own DNA rep, transcrip, and protein synth in the matric using mitochondria-specific proteins encoded by the nuclear genome. 

Replicaiton occurs throughout cell cycle, look to double # of mitochondria by mitosis, not tightly controlled. 

Origin of replication on each strand, mtDNAs chosen at random for replication


Describe the transcription of mtDNA

Both strands transcribed from single promoter on each

Produces 2 giant RNAs, each a transcript of one DNA strand

RNAs cleaved into rRNAs, tRNAs, and mRNAs


Describe the translation of mtDNA

Occurs in matrix

Uses tRNAs and rRNAs encoded in mtDNA

Produces 13 polypeptides - all are subunits of complexes involved in oxidative phosphorylation >>> targeted to inner membrane


What is the function of peroxisomes?

Oxidative degradation - break down a variety of molecules (toxins, alcohol, fatty acids)

Production of H2O2 (RH2 + O2 >>> R + H2O2)

Catalast driven rxns (H2O2 + RH2 >> R + 2 H2O) or (2 H2O2 >> 2 H2O + O2)


Beta oxidation: very long chain fatty acids > acetyl CoA


Synthesis of cholesterol, bile acids, and lipids: ex, plasmalogen for myelin sheaths 


How are proteins imported into peroxisomes?

Post-translationally via specific protein translators


Describe disorders of peroxisome biogenesis

Dramatic loss of peroxisome function due to defects in proteins required for peroxisomal biogenesis - peroxisomes lack many peroxisomal enzymes or absent from cells


Ex. Zellweger syndrome - perox enxymes synthesixed normally but not imported, empty peroxs, lethal in early infancy


Describe deficiency of single peroxisomal proteins...

Less severe phenotype, defect in synth, import, or fxn of one perox protein, partially fxnal peroxs


Ex. X-linked adrenoleukodystrophy (ALD)

perox lack membrane protein involved in degradation of very long chain fatty acids

build up of long chain fatty acids

Leads to demyelination of neurons, dysfunction of NS, adrenal insufficienct

lethal in mid childhood


What are ways to treat X-linked adrenoleukodystrophy?

1. Allogeneic hematopoietic stem cell transplant (HCT) - high morbidity due to complications, compatible donor cells not always available, must be performed at early stage due to brain lesions


2. Gene therapy - Stem cells collected from pt, corrected ex-vivo w/ HIV derived lentivirus, bone marrow eradicated, and own stem cells put back

First successful clinical test of HIV-derived vector