Heart responds to fasting by remodeling vital energy-producing components

November 19, 2004

St. Louis, Nov. 19, 2004 -- Researchers at Washington University School of Medicine in St. Louis have identified a previously unsuspected response by mouse heart muscle cells to fasting conditions: the cells' power generators, the mitochondria, appear to remodel and consume extra internal walls or membranes in an effort to supply energy to the rest of the cell.

Partially consumed are the specialized internal membranes mitochondria use to generate energy-rich compounds for the cell, making the mitochondrial strategy appear to create more problems than it might solve. Nevertheless, the response appears to help maintain healthy heart function throughout caloric restriction.

"It is likely that the changes in the membranes make the mitochondria more energy efficient and serve as an adaptation to nutritional deprivation in mammals," says Richard Gross, M.D., Ph.D., senior author and professor of medicine and director of the Division of Bioorganic Chemistry and Molecular Pharmacology in the Department of Medicine.

The findings, scheduled to be reported in an upcoming issue of the journal Biochemistry and now available through advance online publication, may have implications for human cardiovascular health.

In their studies of mouse heart muscle, the research team found levels of two members of a class of lipids (fatty molecules) called phospholipids fell dramatically when food was withheld. For one type of phospholipid, levels decreased by 20 percent after only four hours of fasting and for the other, levels dropped a remarkable 40 percent after twelve hours of fasting.

The changes in phospholipids occurred mainly in the mitochondria, which are highly abundant in heart muscle cells and account for most of the phospholipid content of the cells. Mitochondria serve to break down many types of fats to produce the high-energy cellular fuel ATP, which is essential for a multitude of cellular processes, including the regular contraction of the heart muscle.

"What we measured was a massive change in heart lipid composition," Gross says. "In part, it confirms what science has come to recognize--mitochondria are quite dynamic and change shape in response to nutritional and hormonal cues. But we are the first to report that mitochondria essentially remodel their own membranes, and thereby their physical properties, by dynamically altering their use of phospholipids."

A phospholipid decrease of the magnitude reported is all the more surprising because phospholipids comprise essential components of all cellular membranes and have previously been thought to be preserved except in cases of extreme starvation.

The researchers' data also reveal that after feeding resumes, the phospholipid levels in heart muscle cells rise back to normal levels, indicating that mitochondria readily rebuild their membranes.

During this recovery period, another class of lipid, triglyceride, a common source of energy for many types of cells, peaks high above its normal level in heart muscle cells. "The rise of triglyceride isn't easily explained by nutritional conditions, because after feeding resumes, the heart shouldn't need to increase its levels of fats. It's as if the heart retains a memory of deprivation and doesn't want to get caught unprepared again," Gross says.

The next step for the research team will be to study the changes in shape and structure of mitochondria and to relate these to changes to lipid metabolism.

The response by heart mitochondria might lend a partial explanation to a pattern discerned in studies of ischemic heart patients, who have restricted blood flow to the heart.

"While we have to be careful in drawing definitive parallels between mouse lipid dynamics and human lipid dynamics, it is interesting to note that the majority of sudden death in ischemic heart patients occurs in the early morning hours when people have typically had a long fast and are subject to a vast array of hormonal influences during the sleep-wake cycle," Gross says. "The alterations in heart muscle energy utilization during fasting may setup a deleterious situation in the hearts of ischemic heart patients."

The research team uncovered the fluctuations in cellular lipids through an innovative new technology they developed called "shotgun lipidomics." As the name suggests, in comparison to other techniques shotgun lipidomics has the speed and coverage of a shotgun blast: From a simple one-step extraction of lipids in tissues, the team can obtain in minutes highly accurate measurements of the various cellular lipids, which previously have been notoriously fragile, time-consuming to analyze and hard to quantify.

"Through the efforts of people in our division like Xianlin Han, who has worked hard to perfect the technology, we have been able to open up fresh avenues of investigation using shotgun lipidomics," Gross says.
Han X, Cheng H, Mancuso DJ, Gross RW. Caloric restriction results in phospholipid depletion, membrane remodeling, and triacylgycerol accumulation in murine myocardium. Biochemistry, 2004.

Funding from the National Institutes of Health and the Mildred and Clark Cox Fund supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Mitochondria Articles from Brightsurf:

Researchers improve neuronal reprogramming by manipulating mitochondria
Researchers at Helmholtz Zentrum M√ľnchen and Ludwig Maximilians University Munich (LMU) have identified a hurdle towards an efficient conversion: the cell metabolism.

Inside mitochondria and their fascinating genome
EPFL scientists have observed -- for the first time in living cells -- the way mitochondria distribute their transcriptome throughout the cell, and it involves RNA granules that turn out to be highly fluid.

'Cheater mitochondria' may profit from cellular stress coping mechanisms
Cheating mitochondria may take advantage of cellular mechanisms for coping with food scarcity in a simple worm to persist, even though this can reduce the worm's wellbeing.

A ribosome odyssey in mitochondria
The ciliate mitoribosome structure provides new insights into the diversity of translation and its evolution.

Fireflies shed light on the function of mitochondria
By making mice bioluminescent, EPFL scientists have found a way to monitor the activity of mitochondria in living organisms.

First successful delivery of mitochondria to liver cells in animals
This experiment marks the first time researchers have ever successfully introduced mitochondria into specific cells in living animals.

Lack of mitochondria causes severe disease in children
Researchers at Karolinska Institutet in Sweden have discovered that excessive degradation of the power plants of our cells plays an important role in the onset of mitochondrial disease in children.

Unexpected insights into the dynamic structure of mitochondria
As power plants and energy stores, mitochondria are essential components of almost all cells in plants, fungi and animals.

Mitochondria are the 'canary in the coal mine' for cellular stress
Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery.

Master regulator in mitochondria is critical for muscle function and repair
New study identifies how loss of mitochondrial protein MICU1 disrupts calcium balance and causes muscle atrophy and weakness.

Read More: Mitochondria News and Mitochondria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.