2 | mitochondria Flashcards
what tasks are mitochondria involved in?
supplying cellular energy
signaling
cellular differentiation
cell death
maintaining control of the cell cycle and cell growth
describe the structure of the mitochondria
outer membrane
—– contains porins and transporters
intermembrane space
inner membrane
—– contains components of the ETC, transporters, and ATP synthase
cristae are invaginations of the inner membrane
matrix
—– contains Kreb’s cycle enzymes, DNA, ribosomes, tRNAs
describe the lipid-protein make up of the mitochondrial membranes
outer membrane
50:50 lipid-protein mixture
inner membrane
20:80 lipid-protein mixture
— lots of integral membrane proteins
— many proteins involved in ETC, oxidative phosphorylation, ATP synthesis, and transport
what is the most abundant protein in the outer mitochondrial membrane?
most abundant protein is a porin called the voltage-dependent anion channel (VDAC), gatekeeper for the entry and exit of mitochondrial metabolites and signaling molecules
briefly describe ATP production via oxidative phosphorylation
pyruvate generated by cytosolic glycolysis is transported into the mitochondrial matrix and converted to acetyl-CoA
the citric acid cycle generates NADH
NADH is transferred indirectly to O2 via the mitochondrial ETC (electrons from NADH reduce O2 to water)
during electron transport, protons, from the mitochondrial matrix are pumped across the inner membrane to create a gradient (build-up of protons)
the resultant proton-motive force and movement of protons back across the IMM is coupled to the synthesis of ATP from ADP by ATP synthase
describe the warburg effect
even tho oxygen is present, cancer cell defaults to glycolysis as its primary way to generate ATP
this information alone can’t be used to treat tumors bc healthy cells like stem cells rely on aerobic glycolysis
glucose –> pyruvate –> lactate + CO2
describe mitochondrial activity and energy production in a cancer/tumor cell
low mitochondrial activity and oxygen consumption
—- the middle of the tumor is deprived of oxygen, so it defaults to the ATP formed from glycolysis (2 ATP each time)
high glucose utilization and lactate production
—- therefore, increased uptake of glucose
—- lack of glucose in blood can be used to diagnose cancer
describe angiogenesis in a cancer/tumor cell
these cells in the middle of the tumor start releasing factors that cause the formation of blood vessels that infiltrate the tumor – called angiogenesis
they deliver oxygen and blood into the tumor
the cells will still rely on glycolysis for their energy… which otto found strange
what about the blood can be used to diagnose cancer?
high glucose utilization and lactate production
therefore, increased uptake of glucose
lack of glucose in blood can be used to diagnose cancer
describe the endosymbiotic origin of mitochondria
approximately 1 billion years ago, mitochondria evolved from bacteria that were engulfed into ancestral eukaryotic cells forming endosymbionts
most of the bacterial genes were lost… some transferred to nuclear chromosomes, some retained by mitochondria
some bacterial derived genes were retained because
—- they encoded polypeptides too hydrophobic to be imported from the cytosol
—- large size of tRNAs too difficult to import
—- regulation of mtDNA genes more flexible and advantageous in response to changing cellular conditions
what drives maternal mitochondrial DNA inheritance?
human egg has approximately 500k mtDNA whereas a sperm has approximately 100
mitochondrial DNA/ mitochondria replicates itself
describe mitochondrial heteroplasmy
mutations can occur in mtDNA and be passed on to daughter cells
cells generally contain mixtures of wild-type and mutant mtDNA known as heteroplasmy
homoplasmic = all wild type or all mutant
heteroplasmic = mix
how is mitochondria transferred between cells?
tunneling nanotubes (TNTs) are tubelike projections of the plasma membrane that connect the cytosol of animal cell
can transfer ions, metabolites, and organelles between cells..
BUT can also transfer mitochondria between cells to help injured cells recover
aka intracellular mitochondrial transfer
—- can be done between different cell types
describe mitochondrial morphology
mitochondrial morphology is quite varied, sometimes tubular branched networks or fragmented and small
unstressed and healthy cells tend to have an extensive network of fused mitochondria (more surface area)
—- therefore, high ATP production
stressed cells have fragmented mitochondria
—- therefore, low ATP production
how is mitochondrial fusion and fission regulated?
regulated by specialized proteins
GTP hydrolyzing enzymes control mitochondrial fission and fusion
—— GTP hydrolyzing enzymes are members of the dynamin family
fusion: integral membrane Mitofusin 1 and 2 (MFN1, MFN2) control fusion of the outer mitochondrial membrane followed by fusion of the inner mitochondrial membrane by OPA1
fission: multiple soluble cytosolic DRP1 is recruited to the outer mitochondrial membrane where it polymerizes to sever the membrane
GTP hydrolysis is required for fusion and fission
describe how fusion for mitochondria is regulated
integral membrane Mitofusin 1 and 2 (MFN1, MFN2) control fusion of the outer mitochondrial membrane followed by fusion of the inner mitochondrial membrane by OPA1
describe how fission is regulated for mitochondria
multiple soluble cytosolic DRP1 is recruited to the outer mitochondrial membrane where it polymerizes to sever the membrane
what happens if calcium enters the mitochondria?
moderate Ca2+ uptake stimulates citric acid cycle activity and ATP production
once inside, calcium can do a number of things, including increasing the activity of enzymes in the krebs cycle (increased NADH, etc. -> increased ATP production via ETC)
—— Ca2+ overload can trigger programmed cell death (apoptosis)
—— influx of calcium (high levels) can cause the mPTP (mitochondrial permeability transition pore) to open
—— when mPTP opens, it allows stuff from the matrix and inter membrane space to get out, one being cytochrome C (from ETC) which can cause problems if in the cytosol, triggering apoptosis
basically, calcium is good but not too much
what regulates the uptake of calcium into the mitochondria?
Ca2+ uptake in mitochondria is mediated by VDAC (into the outer membrane matrix) and the mitochondrial Ca2+ uniporter (MCU) into the inner membrane matrix
