A Novel Medicine to treat Mitochondrial Dysfunction                associated Diseases.


"Mitochondrial diseases are a group of genetic conditions that affect how mitochondria in your cells produce energy. Mitochondria produce most of the energy your body needs. If you have a mitochondrial disease, your cells aren’t able to produce enough energy. There isn’t a cure, but treatment can prevent life-threatening complications."   

https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases


"Cellular metabolism is a complex, integrated process that is supported by key organelles, such as lipid droplets and mitochondria, which engage in numerous energetic and signaling mechanisms.

A better understanding of the dynamics and interactions of such organelles like lipid droplets and mitochondria could advance research in aging, cancer, degenerative diseases or obesity."

Mitochondria Dynamics (nanolive.ch) 


"In the last decade, there has been an increased appreciation for mitochondria as central hubs in diverse processes, such as cellular energy, immunity, and signal transduction. As such, we have become aware that mitochondrial dysfunction underlies many diseases, including primary (mutations in genes encoding mitochondrial proteins) and secondary mitochondrial diseases (mutations in non-mitochondrial genes critical for mitochondrial biology), as well as complex diseases with mitochondrial dysfunction (chronic or degenerative diseases). Evidence suggests that mitochondrial dysfunction may often precede other pathological signs in these disorders, further modulated by genetics, environment, and lifestyle." 

https://www.nature.com/articles/s41598-023-34624-8


"Mitochondrial damage is implicated as a major contributing factor for a number of noncommunicable chronic diseases such as cardiovascular diseases, cancer, obesity, and insulin resistance/type 2 diabetes." 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255501/


"Mitochondrial dysfunction is known to be associated with a wide range of human pathologies, such as cancer, metabolic, and cardiovascular diseases." 

https://www.frontiersin.org/articles/10.3389/fmolb.2021.671908/full


"Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified in central nervous system disorders. Membrane leakage and electrolyte imbalances, pro-apoptotic pathway activation, and mitophagy are among the mechanisms implicated in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as ischemic stroke." 

https://www.nature.com/articles/s41536-020-00107-x


"T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity." , "At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. ", "Collectively, our findings provide a rationale for manufacturing exhaustion-resistant T cell products for clinical use. Since efficient mitochondrial respiration is crucial for the stemness of exhausted T cells, pharmacological and genetic approaches to enhance their mitochondrial fitness and/or restrict their glycolytic metabolism are promising metabolic intervention strategies to maintain (or reinvigorate) their functionality during cancer immunotherapy."

www.nature.com/articles/s41467-023-42634-3#:~:text=At%20the%20molecular%20level,%20we,into%20terminally%20exhausted%20T%20cells. 


"Organismal ageing is accompanied by progressive loss of cellular function and systemic deterioration of multiple tissues, leading to impaired function and increased vulnerability to death. Mitochondria have become recognized not merely as being energy suppliers but also as having an essential role in the development of diseases associated with ageing, such as neurodegenerative and cardiovascular diseases."

www.nature.com/articles/s41574-021-00626-7 


"The interplay between mitochondria and store-operated Ca2+ entry: Emerging insights into cardiac diseases"

https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.16941


"Novel role of the ER/SR Ca2+ sensor STIM1 in the regulation of cardiac metabolism"

https://journals.physiology.org/doi/full/10.1152/ajpheart.00544.2018


"STIM1-dependent Ca2+ microdomains are required for myofilament remodeling and signaling in the heart"

https://www.nature.com/articles/srep25372#:~:text=Besides%20changes%20in%20NCX%20expression,increased%20cytosolic%20Ca2%2B%20concentration.


"A mitochondrion (/ˌmaɪtəˈkɒndriən/; pl. mitochondria) is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used throughout the cell as a source of chemical energy.",  "In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling, cellular differentiation, and cell death, as well as maintaining control of the cell cycle and cell growth. Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes. Mitochondria have been implicated in several human disorders and conditions, such as mitochondrial diseases, cardiac dysfunction, heart failure and autism." 

en.wikipedia.org/wiki/Mitochondrion 

"Video 1: On the left panel you can observe a time-lapse of pre-adipocytes imaged with the 3D Cell Explorer for 1 hour at a frequency of one image per five seconds (movie speed: 15fps). On the right panel we zoomed a portion of the field of view to better appreciate the interactions between mitochondria and lipid droplets. On the two small squares on the bottom, the mitochondria and lipid droplets are displayed for identification at different time points." 

https://www.nanolive.ch/mitochondria/

"Video 2: On the top panel you can observe a time-lapse video of of pre-adipocytes imaged with the 3D Cell Explorer for 1 hour at a frequency of one image per five seconds (movie speed: 15fps). Objective magnification is 60x. On the bottom panels we progressively zoom into the cells to better appreciate all details of these interactions (2x = 120x; 4x = 240x; 8x = 480x), e.g. mitochondria dynamics."

 https://www.nanolive.ch/mitochondria/