Lecture #1 Flashcards
what is the theory stating that an aerobic protobacterium was engulfed by an ancestral eukaryotic cell, conferring oxidative phosphorylation to the ancestral eukaryotic cell?
endosymbiotic theory
what are invaginations in the inner membrane of the mitochondria
cristae
what happens inside of cristae
oxidative phosphorylation
where does the Krebs cycle, beta-oxidation, and steriodogenesis take place?
matrix
what is the main characteristic that makes mitochondria unique?
they posses their own DNA
how are mitochondria are derived?
from the production of membrane from the smooth ER and fission events of pre-existing organelles
what is present on the inner mitochondrial membrane that is not present in the outer mitochondrial membrane?
cardiolipin
how many polypeptides are derived from mitochondrial DNA?
13
describe mitochondrial DNA:
16 kb circular dsDNA with several copies present
what are the packing structures of mitochondrial DNA called?
nucleoids
what does TFAM stand for?
transcription factor A mitochondrial
what is mitochondrial DNA fully dependent on?
nuclear DNA
why is mitochondrial dna fully dependent on nuclear dna?
the machinery needed for its replication, transcription, and translation comes from the nucleus
what is the helicase responsible for unwinding mtDNA allowing for replication?
twinkle
how are mitochondria configured in a cell?
in a elastic network where individual mitochondria are constantly fusing and dividing
how many genes does mitochondrial DNA encode for?
37
describe the two main parts of mitochondrial dna:
heavy strand (outer strand) and light strand (inner strand)
where are the vast majority of genes coded for?
heavy strand
what is the only gene transcribed by the light strand?
ND6
mitochondrial DNA only has __ promotor, making it a _____________
1 ; polycistronic transcript
where is the regulation of the abundance of the mitochondrial mRNA, tRNA, and rRNA established?
at the post-transcriptional level
proteins encoded by mitochondrial DNA are all part of what?
the respiratory chain
what characteristic of mitochondrial proteins does not allow them to be transported via the classical translocons?
they are the most hydrophobic proteins
describe the 3’ end of mitochondrial DNA:
very short poly A tail
what is unique about the 5’ end in mitochondrial DNA?
no capping
what are the three main players in mitochondrial generation?
NRF-1&2 (nuclear respiratory factor), PPAr(alpha) and ERRs (estrogen-related receptors)
what is the key function of NRF-1&2?
important in the transcription of genes encoding for the subunits of the respiratory chain and for TFAM
what is the key function of PPAR(alpha)?
transctiption factor important for the control of the expression of genes of the fatty acid beta-oxidation
what is the key function of estrogen-related receptors?
control the TCA cycle genes, respiratory chain genes, and other oxidative phosphorylation-related genes
what is the main regulator of mitochondrial biogenesis?
PGC-1alpha
what occurs when PGC-1alpha is increased in both a transcriptional and protein level?
it binds to the key three transcription factors promoting both the transcription and translation of mitochondrial genes
what does PGC-1alpha promote besides the transcription and translation of mitochondrial DNA genes?
the transcription and translation of nuclear genes encoding for mitochondrial proteins
what are diseases caused by mutations in the mitochondrial DNA
primary mitochondrial diseases
besides mutations in mitochondrial dna, what can cause primary mitochondrial diseases?
mutations in nuclear genes encoding for mitochondrial proteins
how many pathways exist for the translation of proteins encoded by the nucleus?
three
one pathway for the translation of proteins encoded by the nucleus is mediated by what protein?
PUMILIO1
where does PUMILIO1 bind to?
3’ end of specific mRNAs
what does PUMILIO1 allow for?
the co-translational import of proteins
how are the vast majority of nuclear encoded proteins imported?
in a post-translational manner and imported through chaperones
where is the vast majority of mitochondrial proteins synthesized?
cytosol
what are the 5 major protein import pathways into the mitochondria?
presequence, cystine rich, beta-barrels, carrier proteins, and alpha-helical proteins
what is a presequence?
aminoacidic sequence located in the N terminus
what is the function of a presequence?
unique target that allows for sorting
which specific types of proteins use the presequence pathways as their main form of transport?
matrix proteins and proteins residing in the inner membrane
for what specific types of proteins is a presequence most often NOT present?
proteins in the inner membrane space, outer membrane, and a few in the inner membrane
what specific type of bond can those proteins with cystine residues create?
disulphide bonds
where are the vast majority of proteins with cystein-residues folded? Therefore, what type of pre-sequence do they contain?
inside the ER; an ER pre-sequence
what do proteins that reside in the outer membrane not have?
pre sequences
what are beta-barrel proteins?
very large pores in the membrane that allow for the passage of solutes and ions
where are carrier proteins located?
inner mitochondrial membrane
if there is an alteration of the permeability of the imm, what occurs?
permeability transtion leading to apoptosis
what is the carrier protein passage dependent on?
mitochondrial membrane potential (MMP)
how long is the presequence of mitochondrial proteins?
15-50 amino acids
what does the presequence of mitochondrial proteins form?
an amphipathic alpha-helix
what recognizes the elements of the amphipathic alpha helix on the receptors of the omm?
translocons
what occurs when there is alteration of the permeability of the membrane?
permeability transition
what is the funcitonality of the imm very important for?
the mitochondrial membrane potential
what category does TOM 40 belong to?
beta-barrel proteins
what type of amino acids does TOM40 contain?
both hydophilic and hydrophobic
when approaching the omm where does the protein bind first, and then where does it enter after?
TOM20 then TOM40
what are the translocons of the inner mitochondrial membrane?
TIM complexes
a presequence is followed by a hydrophobic stretch, which signals for what?
signals for the protein to be laterally sorted into the inner membrane
describe the TIM23 SORT pathway:
related to the proteins that are highly hydrophobic and reside in the inner membrane
describe the TIM23 MOTOR pathway:
regards the proteins that are translocated into the matrix (aka the soluble proteins)
what is another name for mitochondrial membrane potential?
protonmotive force
what are the two components of the protonmotive force?
membrane potential and pH
what is the exact value of the mitochondrial membrane potential?
-180mV
what is used to measure the mmp in cells? And specifically, which one?
potential metric dyes ; TMRM
what is used to ensure that the mpp is being measured and not the plasma membrane potential instead?
uncouplers
what is an example of an uncoupler?
FCCP
what does the mitochondrial membrane potential directly activate on the imm?
TIM23 complex
what complex assists TIM23 in sorting a presequence-containing protein into the matrix?
presequence translocase-associated motor (PAM)
for those proteins containing a hydrophobic stretch, what serves as the gate keeper in TIM23 which allows them to be sorted laterally into the imm
Mgr2
what removes the presequence and folds a protein once it has entered into the mitochondrial matrix?
mitochondrial protease peptide (MPP)
what does the MPP do to proteins that have been translocated into the imm?
cleaves their presequences
what chaperone family is prevalent in the mitochondrial matrix that helps proteins fold?
Hsp60
where is Oxa1 located?
imm
what is the main function of Oxa1?
involved in the insertion of mtDNA-encoded proteins into the imm
what is the function of Oxa1 in regards to nuclear encoded proteins?
sorts proteins located on the imm that possess many transmembrane domains
what are the three main characteristics of carrier proteins?
they are very hydrophobic, contain 6 transmembrane domains, and do not have a presequence
what are the two main carrier proteins?
pyruvate carrier and ANT carrier
what are pyruvate and ANT carrier responsible for transporting across the inner membrane?
pyruvate, ATP, ADP
where are the only two places cysteine-rich precursors are found?
intermembrane space and the ER
what is the function of the MIA complex?
oxidizes cysteines in order to form a disulphide bond and allow a protein to reach its final folded conformation
which part of the MIA complex is responsible for carrying out the reaction to form the disulphide bond?
Mia40
the TOM40 channel is an example of which type of import protein?
beta-barrel protein
what is the most important metabolite channel of the outer membrane?
VDAC
describe VDAC:
voltage dependent, anion-selective channel important for the internalization of metabolites
what is the sorting and assembly machinery for the outer membrane which works in tandem with TOM40?
Sam50
what is responsible for inserting alpha-helical proteins into the omm?
MIM complexes
