Just like the body contains lungs, liver, and lymph nodes, so does each of the body's cells contain tiny specialized organs. Perhaps most peculiar among them are lysosomes--bubble-like sacks that act as part recycling bin, part stomach.
Among other things, a lysosome devours cellular debris--and, like a stomach, it needs to be acidic to do its job. In fact, without acidic lysosomes, cells in culture stop dividing and eventually die off.
"We asked a very simple question: Why?" the senior author. Experiments in the lab uncovered an equally simple answer: Iron. It turns out that a cell can no longer access this essential nutrient when the pH within its lysosomes rises.
The discovery, recently described in Molecular Cell, has implications for understanding and treating diseases, including cancer. The story of lysosomes began in 1955, when Christian de Duve, a cell biologist who would later join Rockefeller, first discovered them. In the years that followed, scientists learned that lysosomes carry out multiple jobs inside cells--from engulfing all sorts of cellular garbage and breaking it down for reuse, to relaying biochemical signal and processing nutrients.
In spite of their complex functions, however, most functions of lysosomes are dispensable. When they don't function properly, "the cell somehow finds ways to compensate," the author says.
The critical exception, as shown by the lab's recent findings, is converting iron into its nutrient form. "Processing iron seems to be the one thing cells cannot accomplish without lysosomes," the author says.
A graduate student in the lab, made the discovery after lysosomal acidity of the cells was reduced ' enough to stress them, but not kill them. In responding to this challenge, the cells activated genes involved in the use of iron, while their iron levels dramatically dropped.
Cells don't cope for long without iron, which is needed to make DNA and other essential molecules. When a rise in pH causes iron depletion, cells stop dividing and eventually die. The scientists think this happens because lysosomes free iron from the molecules that transport it, something they do best at a pH of 4 to 5, the approximate acidity of a tomato.
The authors also show that lysosomal dysfunction dramatically alters mitochondrial metabolism and hypoxia inducible factor (HIF) signaling due to iron depletion.
Because lysosomes are known to be essential for cancer-cell proliferation, the discovery suggests a potentially new way to fight tumors: starving them for iron. In recent years, the lab has devised a number of innovative ways to kill cancer cells by blocking their access to essential nutrients; now iron depletion promises to yield yet another weapon in this arsenal of potential drugs.
"In the future, it will be important to determine whether these findings are also relevant in the context of other conditions linked to the loss of acidity, such as lysosomal storage disorders and neurodegenerative diseases," the senior author says. "We believe there are a lot of exciting possibilities out there."
https://www.rockefeller.edu/news/27377-why-cells-need-acidic-lysosomes/
https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30003-4
Why cells need acidic lysosomes
- 2,317 views
- Added
Edited
Latest News
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Addressing both flu and COV…
By newseditor
Posted 26 Mar
How the brain senses body p…
By newseditor
Posted 26 Mar
Other Top Stories
Attention recruits frontal cortex in human infants
Read more
Early life stress in neurons is mediated by epigenetic mechanism
Read more
Negative mood linked to prolonged amygdala activity
Read more
How the brain understands sentences
Read more
Does 'harsh parenting' lead to smaller brains?
Read more
Protocols
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Profiling native pulmonary…
By newseditor
Posted 08 Mar
Publications
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
Integrated plasma proteomic…
By newseditor
Posted 27 Mar
APP antisense oligonucleoti…
By newseditor
Posted 27 Mar
Targeting Erbin-mitochondri…
By newseditor
Posted 27 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar