idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
idw - Informationsdienst
Wissenschaft
MHH researchers have deciphered the signalling pathway that controls the movement of mitochondria within cells during heart development.
Our heart beats around 100,000 times a day – and does so throughout our entire lives. It draws the energy for this from the mitochondria. As the ‘powerhouses of the cells’, they produce 95 per cent of adenosine triphosphate (ATP), the body’s most important energy currency. If the mitochondria are impaired and cannot function properly, the heart muscle cells lack the strength to pump sufficient blood, oxygen and nutrients into the body. Due to its high energy requirements, the heart has the highest mitochondrial density of all organs, accounting for around a third of its cell volume. During heart development, the mitochondria migrate to the so-called sarcomeres. These smallest components of the muscle cell enable contraction and require energy to do so.
Researchers led by PD Dr Christian Riehle, head of the Myocardial Energetics research group at the Department of Cardiology and Angiology at Hannover Medical School (MHH), and Clinic Director Prof. Dr Johann Bauersachs. They have demonstrated that the movement of mitochondria within heart muscle cells is controlled by so-called RHOT proteins. This process plays a key role when the heart grows and is under particular strain. This may also occur during competitive sport, but also during disease-related remodelling processes in the heart muscle, such as following a heart attack. RHOT proteins therefore represent a promising new approach for the treatment of heart failure. The results of the study have been published in the journal ‘Circulation Research’.
Without RHOT, the heart cannot develop
The research team discovered the proteins through a bioinformatic gene analysis. “We saw that a great deal of RHOT1 and RHOT2 is produced in the heart,” says PD Dr Riehle. Until then, the function of the proteins in the heart had been largely unknown. “However, their high abundance was a clear indication to us that they must be responsible for a key mechanism.” The researchers then investigated the biological signalling pathway in a mouse model. “We knocked out the two proteins, RHOT1 and RHOT2, in the heart muscle cells during embryonic development,” explains Dr Natali Froese, a research associate in the group and first author of the study. “As a result, the mitochondria did not migrate to the sarcomeres but instead clustered around the cell nucleus.” Because the mitochondria could no longer bind to the muscle fibre proteins, the sarcomeres lacked the energy for their further development, leading to heart weakness and heart failure.
Important even under increased workload
The researchers also knocked out RHOT1 and RHOT2 in adult mice. Here, however, the loss of these molecular switches did not have the same fatal effect. Although mitochondrial mobility was equally restricted, ATP production at the sarcomeres was maintained. “This means that in mature heart muscle cells, the mitochondria are already at their intended location,” explains Dr Riehle. The migration towards the sarcomeres therefore takes place during embryonic development. The second finding from the study is that RHOT proteins may also play an important role when the heart is under increased workload – for example, following a heart attack, when dead heart muscle tissue is replaced by non-functional connective tissue and the remaining heart muscle cells must compensate for the loss. “In this context, RHOT proteins represent an attractive therapeutic target,” explains PD Dr Riehle. One possibility would be to increase the activity of the RHOT proteins so that more energy is available to the heart muscle cells. A gene therapy approach would be conceivable here.
Possible treatment approach for PPCM
The heart muscle cells are also subjected to greater strain during pregnancy. The heart muscle then enlarges by up to 30 per cent. This is completely normal, but in exceptional cases it can lead to life-threatening peripartum cardiomyopathy (PPCM). This condition can occur in women with previously healthy hearts a few weeks before or after the birth of a child and can lead to severe heart failure and even death within a short period of time. “Our clinic is Europe’s leading PPCM centre with a specialist outpatient clinic that cares for patients through a multi-disciplinary team,” emphasises Professor Bauersachs. The condition is not only treated at the clinic but is also one of its key research areas. “The RHOT proteins could also offer a therapeutic approach here to relieve the strain on the heart muscle cells of pregnant women and protect the heart,” hopes the clinic director.
SERVICE:
Further information is available from Dr Christian Riehle, riehle.christian@mh-hannover.de.
The original paper “RHOT Proteins Link Mitochondrial Motility to Cardiomyocyte Sarcomere Maturation” can be found here: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.125.327297.
Have explained how the powerhouses of heart muscle cells reach their destination (from left): Dr Chr ...
Copyright: Karin Kaiser/MHH
Merkmale dieser Pressemitteilung:
Journalisten
Medizin
überregional
Forschungsergebnisse, Wissenschaftliche Publikationen
Englisch
Sie können Suchbegriffe mit und, oder und / oder nicht verknüpfen, z. B. Philo nicht logie.
Verknüpfungen können Sie mit Klammern voneinander trennen, z. B. (Philo nicht logie) oder (Psycho und logie).
Zusammenhängende Worte werden als Wortgruppe gesucht, wenn Sie sie in Anführungsstriche setzen, z. B. „Bundesrepublik Deutschland“.
Die Erweiterte Suche können Sie auch nutzen, ohne Suchbegriffe einzugeben. Sie orientiert sich dann an den Kriterien, die Sie ausgewählt haben (z. B. nach dem Land oder dem Sachgebiet).
Haben Sie in einer Kategorie kein Kriterium ausgewählt, wird die gesamte Kategorie durchsucht (z.B. alle Sachgebiete oder alle Länder).
