Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Calcium Connections: Penn Researchers Discover Basic Pathway for Maintaining Cell’s Fuel Stores

28.07.2010
Defining of Novel Mechanism Informs Understanding of Cancer, Aging Physiology

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 cells 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 cell metabolism, 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 endoplasmic reticulum is the major reservoir of calcium in cells. The stored calcium is released to adjacent mitochondria through a calcium ion channel 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.

This research was funded by the National Institute of General Medical Sciences, the National Heart, Lung, and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.

Penn’s School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.

Penn Medicine’s patient care facilities include:

The Hospital of the University of Pennsylvania – the nation’s first teaching hospital, recognized as one of the nation’s top 10 hospitals by U.S. News & World Report.

Penn Presbyterian Medical Center – named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.

Pennsylvania Hospital – the nation’s first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and behavioral health.

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>