Calcium connections: Basic pathway for maintaining cell's fuel stores

Jul 27, 2010
These are mitochondria (orange) in close contact with endoplasmic reticulum. The flashes are the localized release of calcium through the IP3 receptor from the endoplasmic reticulum that is taken up by mitochondria to promote the production of ATP. Credit: The image is modified from the original artwork of Odra Noel, with her permission (http://www.odranoel.eu).

University of Pennsylvania School of Medicine researchers have described a previously unknown biological mechanism in cells that prevents them from cannibalizing themselves for fuel. The mechanism involves the fuel used by cells under normal conditions and relies on an ongoing transfer of calcium between two cell components via an ion channel. Without this transfer, cells start consuming themselves as a way of to get enough energy.

"Altered metabolism is a feature of many diseases, as well as aging," says senior author J. Kevin Foskett, PhD, professor of Physiology. "The definition of this essential mechanism for regulating cell energy will have implications for a wide variety of physiological processes and diseases." The investigators describe their findings in the cover article in the most recent issue of Cell.

Most healthy in the body rely on a complicated process called oxidative phosphorylation to produce the fuel ATP. Knowledge about how ATP is produced by the cell's mitochondria, the energy storehouse, is important for understanding normal , which will provide insights into abnormal cell metabolism, as in the case of cancer.

Foskett and colleagues discovered that a fundamental control system regulating ATP is an ongoing shuttling of calcium to the mitochondria from another cell component called the endoplasmic reticulum.

The is the major reservoir of calcium in cells. The stored calcium is released to adjacent mitochondria through a calcium called the IP3 receptor. The researchers found that this calcium release occurs at a low level all the time.

When the researchers interfered with the calcium release using genetic or pharmacological methods, the mitochondria were unable to produce enough ATP to meet the needs of the cell. This indicates that mitochondria rely on the ongoing calcium transfer to make enough ATP to support normal cell metabolism.

In the absence of this transfer, the mitochondria fail to make enough ATP, which triggers an extreme cell survival process called autophagy, or self eating.

"We discovered that this self consumption as a response to the lack of the calcium transfer appears to work in many types of cells, including hepatocytes from the liver, vascular smooth muscle cells, and various cultured cells lines," says Foskett.

Autophagy is important for clearing aggregated proteins from cells, for example in neurodegenerative diseases, and it plays a role in cancer and hypertension. The IP3 receptor plays important roles in the regulation of programmed cell death, a process that is subverted in many cancers, and in neurodegenerative diseases, including Alzheimer's and Huntington's diseases. Calcium release from the IP3 receptor may be at the nexus of neurodegeneration, cancer and the role of cell metabolism gone awry in these broad disease classes.

Explore further: Surprise: Lost stem cells naturally replaced by non-stem cells, fly research suggests

Related Stories

Mechanism explains calcium abnormalities in Alzheimer's brain

Jun 25, 2008

A new study uncovers a mechanism that directly links mutations that cause early onset Alzheimer's disease (AD) with aberrant calcium signaling. The research, published by Cell Press in the June 26th issue of the journal Neuron, provid ...

Calcium may be the key to understanding Alzheimer's disease

Jul 18, 2008

Researchers at the University of Pennsylvania School of Medicine have shown that mutations in two proteins associated with familial Alzheimer's disease disrupt the flow of calcium ions within neurons. The two proteins, called ...

Researchers identify missing target for calcium signaling

Apr 22, 2009

An international study led by Ohio State University neuroscience researchers describes one of the missing triggers that controls calcium inside cells, a process important for muscle contraction, nerve-cell transmission, insulin ...

Recommended for you

For resetting circadian rhythms, neural cooperation is key

2 hours ago

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

Rapid and accurate mRNA detection in plant tissues

3 hours ago

Gene expression is the process whereby the genetic information of DNA is used to manufacture functional products, such as proteins, which have numerous different functions in living organisms. Messenger RNA (mRNA) serves ...

For cells, internal stress leads to unique shapes

22 hours ago

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

Adventurous bacteria

23 hours ago

To reproduce or to conquer the world? Surprisingly, bacteria also face this problem. Theoretical biophysicists at Ludwig-Maximilians-Universitaet (LMU) in Munich have now shown how these organisms should ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

CarolinaScotsman
4 / 5 (1) Jul 27, 2010
What effect does calcium channel blockers have on all this?

More news stories

Fear of the cuckoo mafia

If a restaurant owner fails to pay the protection money demanded of him, he can expect his premises to be trashed. Warnings like these are seldom required, however, as fear of the consequences is enough to ...

Clean air: Fewer sources for self-cleaning

Up to now, HONO, also known as nitrous acid, was considered one of the most important sources of hydroxyl radicals (OH), which are regarded as the detergent of the atmosphere, allowing the air to clean itself. ...

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Thinnest feasible nano-membrane produced

A new nano-membrane made out of the 'super material' graphene is extremely light and breathable. Not only can this open the door to a new generation of functional waterproof clothing, but also to ultra-rapid filtration. The ...