This is the result of a study published in Science Advances, led by Francesco Cecconi, Full Professor of Biochemistry at the Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Medicine at the Università Cattolica, and conducted by Valentina Cianfanelli, Associate Professor at the Department of Science at Roma Tre University and Principal Investigator of the Young Researchers Project at the Gynecological Oncology Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Background

Mitochondria are highly complex cellular organelles, vital for cell survival. They are responsible for producing the energy cells need to survive. Their integrity is associated with several diseases, both widespread, such as Parkinson's, and rare, so-called mitochondrial diseases, which can affect various parts of the body, from muscles to eyes to the brain. Inside cells, there is a delicate balance between old or damaged mitochondria that must be eliminated and new ones that must replace them. In some diseases, however, this balance is disrupted, and if mitochondria are lost in excess, or if damaged organelles accumulate in the cell and are regularly not eliminated, the very survival of the cell is endangered.

In the case of Parkinson's disease, for example, the loss of mitochondria also plays a role in the death of dopaminergic neurons that underlies the disease.

The Study

Experts have discovered that B55 plays a key role in regulating mitochondrial homeostasis.

"On the one hand," Professor Cecconi explains, "it promotes the removal of damaged mitochondria by stimulating mitophagy, a selective process for removing inefficient and potentially dangerous organelles. On the other, B55 acts as a controller of mitochondrial biogenesis, stabilizing the main promoter of new mitochondrial formation.

In this way, B55 not only promotes the degradation of damaged mitochondria, but also prevents excessive production of new organelles, thus maintaining a dynamic balance between mitochondrial elimination and synthesis. It is of great interest," the expert emphasizes, "that both these effects depend on the functional interaction between B55 and Parkin, a central protein in mitophagy mechanisms, implicated in Parkinson's disease.

Professor Cecconi and Cianfanelli explain: it is no coincidence that in our research, using animal models of Parkinson's disease (Drosophila, the fruit flies), "we observed that by reducing B55 levels we can improve both the motor defects and the mitochondrial alterations typical of the disease." This effect requires the presence of the Parkin factor and acts primarily on mitochondrial biogenesis.

The idea could be to develop small molecules capable of penetrating the brain and selectively acting on dopaminergic neurons, counteracting their death.

More generally, a 'universal' drug that regulates the action of B55 could be developed for various mitochondrial diseases characterized by mitochondrial loss, including some mitochondrial myopathies and neurodegenerative diseases, Professor Cecconi explains. Furthermore, the deregulation of mitochondrial quality and number also underlies the plasticity of tumor cells and their ability to resist therapies, so controlling B55 could become a promising approach in oncology.

This is why "our future studies will aim to identify safe molecules and therapeutic strategies to modulate B55 in preclinical and human cellular models, especially in order to analyze the effect of its regulation on other neurodegenerative and mitochondrial diseases," they conclude.

There are two forms of vitamin D supplements available: vitamin D2 and vitamin D3. Researchers have found that taking vitamin D2 supplements can lead to a drop in the body's concentration of vitamin D3, which is the form our bodies naturally produce from sunlight and use most effectively to raise overall vitamin D levels.

The study, published in Nutrition Reviews, analysed data from randomised controlled trials and found that vitamin D2 supplementation resulted in a reduction in vitamin D3 levels compared to those not taking a vitamin D2 supplement. In many of the studies, the vitamin D3 levels went lower than in the control group.

Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey's Nutrition, Exercise, Chronobiology & Sleep Discipline, said:

"Vitamin D supplements are important, especially between October and March, when our bodies cannot make vitamin D from sunlight in the UK. However, we discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 in the body, which is a previously unknown effect of taking these supplements. This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2."

Professor Cathie Martin, Group Leader at the John Innes Centre, said:

"This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK."

This research supports a previous study published in Frontiers in Immunology, led by Professor Colin Smith from the University of Surrey, which suggests that vitamin D2 and D3 do not have identical roles in supporting immune function. Vitamin D3 has a modifying effect on the immune system that could fortify the body against viral and bacterial diseases.

Professor Colin Smith said:

"We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signalling system in the body -- a key part of the immune system that provides a first line of defence against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body."

Further research into the different functionalities of vitamin D2 and D3 should be a priority in deciding whether vitamin D3 should be the first-line choice of vitamin D supplement, subject to individual requirements.

Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, said:

"Vitamin D deficiency represents a significant public health concern, especially during the winter months with significant deficiency across the UK population. This collaborative research effort aligns well with the Quadram Institute's mission to deliver healthier lives through food innovation to enhance the nutrient density of the food we eat. Tackling this with the most effective form of vitamin D supplementation or fortification is of the utmost importance to the health of the nation."