Mitochondrial proteins

You can still be celebrated, even if you're buried in mud. A new study shows that innumerable other bacteria flock around cable bacteria in the oxygen-free seabed in something that looks like a dance. They apparently use the cable bacteria as an electrical lifeline for oxygen. Video recordings show that the dance stops abruptly if you cut the cable bacteria in half. You can still be celebrated, even if you're buried in mud. A new study shows that innumerable other bacteria flock around cable bacteria in the oxygen-free seabed in something that looks like a dance. They apparently use the cable bacteria as an electrical lifeline for oxygen. Video recordings show that the dance stops abruptly if you cut the cable bacteria in half. The party-poopers cutting the cable bacteria are researchers from the Center for Electromicrobiology (CEM) at Aarhus University. The centre's work focuses on unravelling the mysteries of how cable bacteria work. Cable bacteria are centimeter long, wire-shaped bacteria equipped with internal wiring that transports electrons between oxygen-rich and oxygen-free "dead" zones in the muddy seabed. The first person to stop the dance was PhD student Jesper Jensen Bjerg. Many years ago, he was sitting in a laboratory at the University of Vienna, struggling to follow the transport of electrons in cable bacteria by measuring the differences in the amount of electrons present in the bacteria's cytochrome proteins. (The protein is important for the energy metabolism of cells.) "As I became more and more impatient, I suddenly discovered something unexpected in the microscope: Hundreds of different bacteria flocked around the part of a cable bacteria that was in an oxygen-free environment. It looked like they were dancing and having a great time," says Jesper Jensen Bjerg, who is now a postdoc at CEM. He later discovered that the party stopped when he cut the cable bacteria with a laser. Years of effort His discoveries led to years of effort by the researchers at CEM to explain the phenomenon. And they have now published their preliminary results in the journal Nature Communications. The interesting thing is not the party culture of bacteria, but what happens chemically/physically between the cable bacteria and their tiny neighbours, and what each of them get out of the interaction. "The smaller bacteria are all aerobic, i.e. they need oxygen, and they obviously benefit greatly by transferring electrons to the cable bacteria and thereby getting an electrical connection to oxygen. But we don't yet know how the electrons are actually transferred to the cable bacteria. And we don't know how this affects the cable bacteria. Does it benefit or harm them? Or doesn't it matter to them at all?" says Professor Andreas Schramm, deputy director of CEM. Lots of questions ahead However, the research group has shown that the small bacteria are metabolically active and that the cytochromes in their cells are more oxidized (in other words, release electrons) when they are close to a cable bacteria. This means that the small bacteria are carrying out extracellular electron transfer (EET). But the discovery of the party in the mud raises more questions than it has so far answered. The researchers themselves list the questions in their scientific article:

A research team has identified a molecular target that could open up new therapeutic options to treat aging-associated diseases like Parkinson's. Scientists at the University of Cologne have discovered how cells can eliminate mutated mitochondrial DNA (mtDNA). Mitochondria are the powerhouses of our cells. Due to their evolutionary descent from bacteria, they still have genetic material packaged in chromosome-like structures (nucleoids). They convert the chemical energy in our food into a biologically usable form. A team of researchers from the University of Cologne's Physiology Centre at the Faculty of Medicine, the Centre for Molecular Medicine Cologne (CMMC) and the CECAD Cluster of Excellence for Aging Research has now shown that mutations of the mtDNA lead to a local rearrangement of proteins in the mitochondrial membrane. The mutated mtDNA is targeted, eliminated, and subjected to autophagy, the cellular 'waste disposal'. The results have appeared in Nature Communications under the title 'Mitochondrial membrane proteins and VPS35 orchestrate selective removal of mtDNA'. In many tissues, mutations in mtDNA accumulate as a result of normal aging. These kinds of mutations are an important cause of many aging-associated diseases. There are thousands of copies mtDNA in every cell, so mitochondrial function is only impaired when the percentage of mutated mtDNA molecules exceeds a certain threshold value. It has long been established that mitochondrial damage, including acute mtDNA damage, triggers the process of mitophagy. In this process, dysfunctional mitochondrial parts are selectively degraded and recycled. Dr David Pla-Martin, the lead author of the current study, explained the details: 'What is new in our study is that this mechanism does not affect the cells' endowment with mitochondria, but only clears out the damaged mtDNA. By labelling neighbouring proteins -- so-called proximity labelling -- we showed that mtDNA damage leads to the recruitment of endosomes in close proximity to nucleoids.' Their removal is coordinated by the interaction of the nucleoid protein Twinkle and the mitochondrial membrane proteins SAMM50 and ATAD3. ATAD3 controls their distribution, SAMM50 induces the release and transfer of the nucleoid to the so-called endosomes. 'This additionally prevents the activation of an immune response. The protein VPS35, the main component of the retromer, mediates the maturation of early endosomes into late autophagy vesicles, where degradation and recycling ultimately take place,' said Pla-Martin. Using a mouse model in which mtDNA mutations lead to impaired muscle regeneration, the scientists also showed that selectively mutated mtDNA can be removed by stimulating the activity of the autophagy mechanism with rapamycin. The total number of mtDNA copies thus remains constant, preserving mitochondrial function. Group leader Professor Dr Rudolf Wiesner added: 'Mutations in the genes that code for these proteins lead to severe neurological diseases, in VPS35 for example Parkinson's disease. We now want to use these proteins as new molecular targets to open up entirely new treatment options for these kinds of aging-associated diseases.' Although the road to therapeutic application could still be long, the research team sees a promising approach here.

JV Targets Potential Drugs for Cancers and Infectious Diseases Tel Aviv, Israel, June 15, 2022 (GLOBE NEWSWIRE) -- SciSparc Ltd. (Nasdaq: SPRC) (the "Company" or "SciSparc"), a specialty, clinical-stage pharmaceutical company focusing on the development of therapies to treat disorders of the central nervous system, today announced the appointment of Prof. Ciro Leonardo Pierri as special advisor for MitoCareX Bio Ltd. ("MitoCareX Bio"), SciSparc’s recently established joint venture ("JV") for the discovery and development of potential drugs for cancers, infectious diseases and other life-threatening conditions. Prof. Pierri is a biochemist and serves as an associate professor at the University of Bari, Italy. Prof. Pierri has a broad background in chemistry and biochemistry, with specific expertise in key research areas of structural biology, molecular modeling, and cell physiology. Prof. Pierri’s work has been published in many scientific papers. “This is an exciting period,” said Prof. Pierri. “During the last decade, multiple studies have shown the involvement of mitochondrial carriers (i.e., transporters) in various types of diseases, which makes them interesting research candidates. MitoCareX Bio has taken a step forward, trying to discover potential small molecules that can specifically interact with those carriers and by that to possibly attenuate the disease progression,” concluded Prof. Pierri. The JV focuses on investigating mitochondrial carriers, as the transport of proteins is crucial for cell viability. Because of mitochondrial carriers' significant role in transporting necessary metabolites for cell functioning across the inner mitochondrial membranes, the Company believes that various infectious diseases and life-threatening conditions, such as cancers, might be treated by regulating the function of mitochondrial carriers. In humans, the mitochondrial carrier family (Solute Carrier Family 25, SLC25) consists of 53 members and is the largest solute transporter family. MitoCareX Bio's innovative research will partly build upon successful proof-of-concept experiments performed in the UK. About SciSparc (NASDAQ: SPRC): SciSparc Ltd. is a specialty clinical-stage pharmaceutical company led by an experienced team of senior executives and scientists. SciSparc’s focus is on creating and enhancing a portfolio of technologies and assets based on cannabinoid pharmaceuticals. With this focus, the Company is currently engaged in the following drug development programs based on THC and/or non-psychoactive cannabidiol (CBD): SCI-110 for the treatment of Tourette syndrome, for the treatment of Alzheimer's disease and agitation; SCI-160 for the treatment of pain; and SCI-210 for the treatment of autism spectrum disorder and status epilepticus. Learn more at https://scisparc.com/. Forward-Looking Statements: This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 and other Federal securities laws. For example, SciSparc is using forward-looking statements when it discusses the focus of its JV on discovery, research and development of potential drugs for infectious diseases, cancers and other life- threatening conditions and in investing in new innovative research on mitochondrial carriers and the impact on treatment of cancers and other life-threatening conditions. Historic results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials will suggest identical or even similar conclusions. Because such statements deal with future events and are based on SciSparc's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of SciSparc could differ materially from those described in or implied by the statements in this press release. The forward- looking statements contained or implied in this press release are subject to other risks and uncertainties, including those discussed under the heading "Risk Factors" in SciSparc's Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (the “SEC”) on April 28, 2022, and in subsequent filings with the SEC. Except as otherwise required by law, SciSparc disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events or circumstances or otherwise. Investor Contact: IR@scisparc.com Tel: +972-3-6167055