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!
International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine
New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Power and Electrical Engineering
24.10.2016 | Life Sciences
24.10.2016 | Life Sciences