Cardiac arrhythmias affect a high proportion of the aging population. Mitochondria are the ‘powerhouses of the cells’, and scientists in Cologne have now shown that even a few heart cells with reduced mitochondrial function are sufficient to trigger arrhythmias.
Mitochondria are cell organelles that are involved in many functions. They are considered to be the ‘powerhouses of the cells’ because they convert nutrients into energy.
They are involved in the regulation of programmed cell death, when a cell is no longer needed or even constitutes a risk to the body. Mitochondria have their own DNA (mitochondrial DNA, mtDNA), which accumulates point mutations in its sequence or loses large portions (mtDNA deletions) during the aging process.
If the number of altered mtDNA copies increases too much, there is a dramatic disruption of mitochondrial function and, as a result, of cell function. This phenomenon occurs in individual cells in many organs during the aging process, giving rise to a ‘tissue mosaic’ of a few isolated cells with mitochondrial dysfunction scattered amongst many normal cells.
Until recently it was not clear whether these few cells with defective mitochondria could be responsible for the loss of tissue and organ function associated with aging. Working in Prof. Rudolf Wiesner’s research team in Cologne, Dr. Olivier Baris and his co-workers looked at this tissue mosaic more closely in the context of cardiac arrhythmias.
Taking an experimental approach to the problem, the Cologne scientists used mice that express a mutated mitochondrial protein specifically in the heart as model organisms. The normal protein is required for proper mtDNA replication. In the clinic, the same mutation in patients leads to the accumulation of mtDNA deletions and severe neurological disease. Dr. Olivier Baris and his fellow scientists decided to investigate the heart because this organ is particularly dependent on mitochondrial energy production.
Dr. Baris: “The incidence of cardiac arrhythmias increases dramatically with age and contributes significantly to morbidity and mortality in the elderly.” Indeed, the mutated protein in the mouse heart was shown to cause the accumulation of mtDNA deletions and the development of a tissue mosaic.
Analysis of long-term electrocardiogram recordings in 18-month-old mice showed typical cardiac arrhythmias that are similar to those described in elderly people (spontaneous premature heart beats and blocks of the conduction of the electrical wave), and which intensify under stress. No such increase in arrhythmias was observed in 12-month-old mice that had three times fewer cells with mitochondrial dysfunction.
The results show promise for future new therapeutic approaches. As Dr. Baris concludes: “Our research has shown that the proportion of heart cells with impaired mitochondrial function has to exceed a threshold value in order to cause a functional disturbance of the organ.
A significant finding was that no other signs of cardiac dysfunction (increased scarring, dilatation of the heart or reduced pump function) were found in the mutated hearts.
We therefore showed that indeed the characteristic tendency towards arrhythmias in aging human hearts could be induced by the random accumulation of defective mitochondria in a few isolated cells and the resultant tissue mosaic.
The challenge of the future is to understand how altered mitochondrial function in just a few heart cells impacts the function of the entire organ. The scientists expect that it will be possible to develop new pharmacological treatment strategies for this aging-associated electrical conduction disorder in the heart – important new findings in aging research from CECAD.
Dr. Olivier Baris
CECAD Cluster of Excellence
University of Cologne
Phone +49 221 478-7901
Astrid Bergmeister MBA
Head of CECAD PR & Marketing
CECAD Cluster of Excellence
University of Cologne
Phone + 49 (0) 221-478 84043
Astrid Bergmeister | idw - Informationsdienst Wissenschaft
Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
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
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...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
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...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Power and Electrical Engineering
25.09.2017 | Health and Medicine
25.09.2017 | Physics and Astronomy