New Data sheds light on genesis of our body’s powerhouses

The mitochondria and its protein making “plants” – mitoribosomes

Scientists uncover for the first time how the body’s energy makers are made using Cryo-Electron Microscopy (cryo-EM) at eBIC within Diamond.

A new paper, published in Science on the 19th February, by an international team of researchers reports an insight into ‘the molecular mechanism of membrane-tethered protein synthesis in mitochondria’. This is a fundamental understanding of how the human mitoribosome functions and could explain how it is affected by mutations and deregulation that lead to disorders such as deafness and diseases including cancer development. 

Mitochondria are intracellular organelles which serve as tiny but potent powerhouses in our body. They use oxygen which we inhale and derivatives from food we eat to produce more than 90% of our energy, and therefore effectively support our life. Mitochondria are particularly important in high-energy demanding organs such as heart, liver, muscles and brain. For example, almost 40% of each heart muscle cell is made up of mitochondria.

Read more on the Diamond website

Image: The mitoribosome is attached to its membrane adaptor as it synthesises a bioenergetic protein (glow yellow).

Credit: Dan W. Nowakowski and Alexey Amunts

ALBA collaborates in the discovery of a new muscular disease: myoglobinopathy

An international collaboration led by IDIBELL identifies the first disease caused by a mutation in myoglobin.

At the MIRAS beamline of the ALBA Synchrotron they could demonstrate the presence of oxidized lipids in the damaged muscle cells.
Researchers of the Bellvitge Biomedical Research Institute (IDIBELL) led by Dr. Montse Olivé have described in Nature Communications a new muscular disease caused by a mutation in the myoglobin gene. The study has been possible thanks to a collaboration with a group of geneticists from the University of Western Australia (UWA), led by Prof. Nigel Laing, and researchers from the Karolinska Institute (Stockholm, Sweden).

Myoglobin, the protein that gives muscles their red colour, has as its main function the transportation and intracellular storage of oxygen, acting as an oxygen reservoir when there are low levels (hypoxia) or a total lack thereof (anoxia). It also acts as scavenger of free radicals and other reactive oxygen species, avoiding cell damage due to oxidative stress.

>Read more on the ALBA website

Image: Left, Typical μFTIR spectra and their second derivative of the muscle tissue where the lipid region has been highlighted in orange and the protein region in blue; the inset shows the lipid/protein ratio (calculated from the Infrared spectra) on an optical image of a tissue section with sarcoplasmic bodies. The color bar represents intensity of the ratio: blue and red mean low and high lipid content, respectively. The scale bar is 4 microns. Right,  Infrared second derivative spectrum of the amide region of one sarcoplasmic body (green) showing an increase of β-sheet structures indicating protein aggregation. Second derivative of the amide region corresponding to the tissue surrounding the sarcoplasmic bodies (black).

Synchrotron light unveils new insights about amytrophic lateral sclerosis

Synergetic combination of different imaging and spectroscopic synchrotron techniques performed in ALBA and APS (USA) has discovered new aspects about astrocytes cells of this neurodegenerative disease.

Results, published in Analytical Chemistry, show significant differences between ALS and control astrocytes, including structural, chemical and macromolecular anomalies. Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that causes the degeneration and death of neurons that control voluntary muscles. Still today the causes of this disease are unknown in 90% of the cases. However, some of them are caused by the mutation of sod1 gene. This gene encodes an enzyme (SOD1) that is involved in cellular protection against oxidative stress. Mutations dramatically alter the biochemical properties of SOD1, in particular its metal binding affinity and its anti-oxidative activity levels. But it is still unknown how these mutations block the normal cell function and lead to death of motor neurons. The ALBA Synchrotron, in collaboration with researchers from the University of Belgrade Pavle Andjus and Stefan Stamenković (who accomplished his PhD thesis using these results) and Vladan Lučić from Max Planck Institute of Biochemistry (Germany), has studied with synchrotron light techniques and classical biochemical laboratory approaches the cellular structural and biochemical changes of this gene mutation in a transgenic animal model of ALS. In particular, scientists have analysed astrocytes, one kind of brain cells that are key players in pathological processes of this disease.

>Read more on the ALBA website

Image: Researcher Tanja Dučić during the experiment performed at ALBA, at the MIRAS beamline.

Structure reveals mechanism behind periodic paralysis

The results suggest possible drug designs that could provide relief to patients with a genetic disorder that causes them to be overcome suddenly with profound muscle weakness.

A rare genetic disorder called hypokalemic periodic paralysis (hypoPP) causes sudden, profound muscle weakness in people who occasionally exhibit low levels of potassium in their blood, or hypokalemia. When a patient is hypokalemic, hypoPP affects the function of the muscles responsible for skeletal movement. The disease has been known to stem from mutations in certain membrane proteins that channel and regulate the flow of sodium into cells. Exactly how the mutation affects the proteins’ function, however, was not known.

In earlier work, researchers from the Catterall Lab at the University of Washington had solved the structure of a sodium channel called NavAb from a prokaryote (single-celled organism). As a next step, the group decided to see if NavAb could serve as a model for studying the mutations that cause hypoPP in humans (eukaryotes), with the goal of finding a way to prevent or treat this disorder.

A leak in the pipe?

In a resting state, muscle-cell membranes keep potassium ions and sodium ions separated, inside and outside the cell, respectively, creating a voltage across the membrane. A chemical signal from a nerve cell sets off a cascade of events that results in sodium ions flowing into the cell, changing the membrane potential and and ultimately triggering muscle contraction.

>Read more on the Advanced Light Source website

Image: Three states of the voltage-sensing domain (VSD) of a membrane-channel protein. In the normal state, the water-accessible space (magenta) does not extend through the channel, preventing sodium (gray spheres) from passing through. In the disease state, a clear passage allows sodium to leak through, resulting in muscle paralysis. In the “rescued” state, the binding of guanidinium (blue and yellow spheres) effectively closes the channel and blocks sodium leakage. The red sphere represents the location of the disease-causing mutation. The side-chain sticks represent the voltage sensors of the sodium channel.