Lecture 17: Cancer as a Metabolic Disease Flashcards
what part of the mitochondria is abnormal in cancer
missing cristae → can’t conduct oxidative phosphorylation → cells need to ferment (get energy from a non-oxidative source)
which high profile people did GBM mitochondria kill
Ted Kennedy, Bo Biden, John McCain
all major cancers have abnormalities in the number and structure of mitochondria. how do those cells survive? what energy do they need to grow?
- fermentation, which is ATP in hypoxia (“w/o oxygen”)
- because they have abnormalities in their mitochondria structure and function
role of mitochondrial lipids in electron transport chain function
every tumor has an abnormal composition of cardiolipin
abnormal composition/distribution of cardiolipin > disrupts ETC’s structure/efficiency in producing ATP through oxidative phosphorylation
role of cardiolipin:
cardiolipin in the inner mitochondrial membrane stabilizes and organizes key ETC protein complexes to ensure efficient electron transfer and ATP production
tumors and cardiolipin abnormalities:
in cancer cells, cardiolipin often has an abnormal composition or distribution. this can disrupt the ETC’s structure and reduce its efficiency in producing ATP through oxidative phosphorylation
inefficient oxidative phosphorylation in cancer:
most cancers rely more on glycolysis for energy (even in oxygen’s presence, known as the Warburg effect) because their oxidative phosphorylation is inefficient, partly due to defective cardiolipin
cardiolipin
lipid enriched in the inner membrane of the mitochondria
where and when else does the body ferment?
- RBCs
- muscle cells (for a bit)
- after a heart attack (the body will temporarily ferment because it will be filled with lactic acid and succinic acid instead of blood)
carcinogen: what is it and how does it impact mitochondria?
- cancer-causing chemical
- enters mitochondria and inhibits it from producing energy efficiently
reactive oxygen species (ROS)
- chronically damages the ability of the mitochondria to function
- carcinogenic
- mutagenic (“the ability to cause a permanent change in an organism’s genes”)
sleep apnea
not breathing sometimes while sleeping > intermittent hypoxia > damage to oxidative phosphorylation > development of dysregulated cell growth driven by fermentation (must happen chronically (“all the time”) in order for this to happen though)
C reactive protein
- marker in blood for inflammation
- significant relationship between obesity and cancer
what are the consequences of chronic inflammation
chronic inflammation > damage in oxidative phosphorylation > mitochondria becomes damaged > over time, the mitochondria relies on fermentation
BRCA1 mutation
mutation that damages oxidative phosphorylation
* Angelina Jolie removed her breasts because she had this gene for breast cancer
why does the dogma state that cancer a genetic disease?
many cancers have mutations in the nucleus
where do the mutations in cancer come from?
the reactive oxygen species (ROS) produced by the abnormal mitochondria. the mutations aren’t the cause of cancer, but an effect of cancer
dogma vs. reality of cancer theory
dogma: mutations in the nucleus cause disregulated cell growth
reality: the reactive oxygen species (ROS) produced in the mitochondria cause the mutations