Yet another study, which demonstrates the inseparable link between metabolism and “structural” problems such as cellular integrity and lifecycle (e.g. apoptosis), as well as mysterious processes of systemic inflammation, often occurring without any cause that medicine can identify. Both of these processes are highly visible in cancer – i.e. lack of apoptosis in “cancer” cells despite their wrecked genome and metabolic dysfunction, as well as their highly inflamed nature that “recruits” nearby cells to the “cancer” process through the cytokines the “cancer” cells produce and releases in the blood. In other words, all that takes for systemic inflammation and even cancer (i.e. lack of apoptosis in damaged cells) to form is reduced mitochondrial function, resulting in a prolonged drop of ATP levels. Thus, chronic stress, inflammatory diet (PUFA anyone?), endocrine disruptors, and the “modern” life characterized by never-ending soul-crushing routines are all direct causes of all our ailments as the one thing all those pathological processes have in common is their profoundly suppressive effects on mitochondria/OXPHOS. Conversely, simply restoring/improving mitochondrial function may be enough to ameliorate/cure virtually all chronic diseases known to medicine. It is also worth noting that reduction of the ATP/AMP ratio (by lowering ATP) and thus activation of AMPK is currently all the rage in medicine and longevity research, with methods such as fasting, low-carb diets, exhaustive exercise, taking AMPK-mimetics such as metformin, etc being hailed as the key to a very long and healthy life. Yet, behind the scenes, all those interventions may be working to destabilize the organism by increasing baseline inflammation and risk of cancer by lowering mitochondrial production of ATP.
http://dx.doi.org/10.1016/j.immuni.2024.10.012
https://www.sciencedaily.com/releases/2024/11/241126134956.htm
“…”We found that mitochondria provide a kind of decision-making aid: they regulate whether a cell undergoes clean, silent apoptosis or releases pro-inflammatory messenger substances,” explains Prof. Dr Olaf Groß, head of the study, a scientist at the Institute of Neuropathology at the Medical Center — University of Freiburg and a member of the Cluster of Excellence CIBSS — Centre for Integrative Biological Signalling Studies at the University of Freiburg.”
“…The universal “fuel source” for cellular activity is ATP (adenosine triphosphate). If the ATP in the mitochondria drops sharply, a protein important for apoptosis, known as cytochrome c, remains trapped in the mitochondria and the cell does not die, even if it receives the signal to do so from outside. Instead, the mitochondria activate mechanisms that trigger an inflammatory response, which puts the tissue on alert and prepares it for a possible threat. The researchers have now discovered that a special “sensor” in the cells, known as NLRP3, is activated when the mitochondria cease energy production. However, a second signal from other areas of the cell is needed to activate the NLRP3 sensor. This so-called “two-signal mechanism” ensures that inflammation is only triggered in the event of serious danger, thus protecting healthy cells. This enables the body to react to threats in a targeted manner while at the same time preventing unnecessary inflammation that could damage the tissue. This discovery could be helpful for the treatment of diseases in which inflammatory processes play a role — such as gout, type 2 diabetes or severe cases of COVID-19. “In the future, drugs could be specifically designed to mitochondria or the activation of NLRP3 in order to better control inflammation and, on the one hand, to prevent damage to healthy tissue and, on the other, to promote the immune response to infection or the rejection of cancer by the immune system,” says Groß.”
