The crosstalk between mitochondria and lipid droplets and its influence on aging

In our current project dealing with lipid droplets we are on the scent of the secrets of mediterran kitchen. With justification it is rumored, that it can reduce the risk of cardiac infarctions or of sustaining a stroke. In general it leads to a healthier and prolonged life. With the last mentioned statement we like to continue our course, thats why we have set our focus on olive oil as a central component of the mediterran lifestyle. This oil is rich in oleic acid, which leads to an increase of a specific organelle inside the cell, namely lipid droplets due to excessive consume of it. These simple oil drops are real communication wonders, because they can get in direct physical touch with most of the cell organelles. Recently we were able to demonstrate, that lipid droplets are able to engulf damaged cell components, fatty acids as well as proteins. Due to that fact they are able to heal mitochondria, also known as the power plants of the cell. The necessity of cleaning mitochondria is essential for the cell. Despite of producing energy in form of ATP, mitochondria are also dangerous to the cell. With the continuous production of oxygen radicals mitochondria bare a self-harming behavior. It is assumed that these oxygen radicals and the resulting cellular damages contribute mainly to the aging process (notwithstanding that this thesis was relativized a modicum of its significance years ago). These oil drops we are investigating at the moment, are capable to remove and incorporate damaged proteins. In a selfless act lipid droplets that have engulfed potential harmful proteins get degraded on their own. As a result lipid droplets are in the position of rejuvenating aged and inadequate functioning mitochondria. A doubling of the amount of lipid droplets results in a roughly 50 percent prolonged life span. The exact molecular and cell-biological mechanisms that inhere the dramatic increase of the life span will be part of this project. For this reason we flare a broad spectrum of molecular-biological and cell-biological methods with generating genetically modified organisms and generation of proteins, which have never seen bevor in this manner, for the investigation of intracellular events via fluorescence microscopy.

An important element in the aging process is an increase in oxygen radicals, which mainly originates from the mitochondria and damages many cellular components. These damaged structures include proteins. These are unfolded under the influence of oxygen radicals or change their structure strongly, so that they have an increased tendency to aggregate. This leads to the well-known aggregates in the aging process, which have proven to be a driving force of neurodegenerative diseases. In addition to the proteins, however, the source of the oxygen radicals, the mitochondria themselves, is also damaged, which leads to strong morphological changes in this cell organelle and thus to an increased output of oxygen radicals. A vicious circle that greatly accelerates cellular aging. In our project, we were able to show that there is a new way to control this multifaceted cellular damage. In fact, another cell organelle can be found in the cell, which is called lipid droplet (LD). As the name implies, the LD consists predominantly of fat and until recently was only considered a cellular fat store. However, the widespread acceptance of the storage theory is only one aspect of the function of the organelle. In recent decades, however, more and more functions have been assigned to LDs bit by bit. In this project, we were able to show that specific proteins are taken up by the LDs. In addition, the LDs have a certain affinity for protein aggregates. These protein aggregates are formed under the influence of oxygen radicals, stress, as well as in the process of cell aging. LDs help to dissolve or break them down. There are also a wide variety of protein aggregates, all of which interact directly or indirectly with the LDs or are associated with them. This indicates that these organelles play an important role in managing age-related stress. Using one of the most important model systems in molecular biology, the yeast cell, we were able to show that stimulating the LD amount has a positive effect on cellular fitness. Using modern fluorescence microscopes, we were able to observe that, triggered by a mitochondria-LD interaction, protein aggregates detach from the mitochondrial membranes and are subsequently bound by the LDs. This helps to regenerate mitochondrial morphology and rejuvenate the mitochondria. This mechanism also has positive effects on the entire cell. Stress resistance increased and the lifespan of the yeast cell was significantly extended. It is noteworthy that, in addition to the genetic modifications made, the addition of oleic acid, one of the main components of olive oil, can also stimulate the amount of LD. It can therefore be speculated that the described life-prolonging effect of the Mediterranean diet, especially olive oil, could be due to the LDs.