Mitochondria, the powerhouses of the cell, are crucial for a variety of cellular processes, including energy production, apoptosis, and cellular signaling. In some cases, viruses, bacteria, and fungi can directly interact with mitochondria, altering mitochondrial membrane potential and inducing oxidative stress. Viral and bacterial infections can lead to the release of pro-inflammatory cytokines, which can contribute to mitochondrial dysfunction. Some bacteria have evolved mechanisms to directly target and manipulate mitochondrial function, which can impact immune response and disease outcome. Hepatitis B virus (HBV), HIV, Zika virus, and influenza virus are some of the viruses that lead to mitochondria dysfunction. S. aureus, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Salmonella enterica, Chlamydia trachomatis, and Escherichia coli are some of the bacteria that have been found to impact mitochondrial function. Some fungal pathogens can produce toxins that directly target mitochondrial function. A. fumigatus produces toxins that target mitochondria, leading to oxidative stress and mitochondrial dysfunction. Another example is Candida albicans has been shown to produce toxins that target mitochondrial function, leading to impaired cellular respiration and reduced ATP production.
Mitochondrial permeability transition pore (mPTP) openings.
The mitochondrial permeability transition pore (mPTP) is a protein complex located in the inner mitochondrial membrane that plays an important role in regulating mitochondrial function. The mPTP is a non-specific channel that can allow the passage of small molecules, including ions and proteins, across the mitochondrial membrane. Opening the mPTP can cause several changes in mitochondrial function, including a decrease in mitochondrial membrane potential, a release of stored calcium, and an increase in mitochondrial swelling. In response to certain stimuli, such as oxidative stress or calcium overload, the mPTP can open, leading to mitochondrial dysfunction and cell death which has been implicated in several diseases, including neurodegenerative diseases, cardiac ischemia-reperfusion injury, and sepsis. Under normal conditions, the mPTP remains closed, which is important for maintaining proper mitochondrial function. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS but also by pro-apoptotic signals that are induced by DNA damage.
Increased mPTP opening has been observed in COVID-19 patients, which may contribute to the severity of the disease. SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. M protein of SARS-CoV2 transduction increased mPTP opening. Pharmacological inhibition of mPTP opening was sufficient to prevent insulin resistance. mPTP dysfunction can have a negative impact on mitochondrial DNA (mtDNA), which is located within the mitochondrial matrix.
Diabetes after SARS-CoV2 infection or vaccination.
A recent study showed that the chance of SARS-CoV-2 infection was associated with a higher risk of diabetes. Among males, SARS-CoV-2 infection was associated with a significantly higher risk of incident diabetes. Further examination by COVID-19 severity, the overall and sex-specific adjusted risk of incident diabetes was higher among people with more severe disease, including individuals admitted to the ICU or hospital. CDC stated that people younger than 18 with COVID-19 were up to 2.5 times more likely to be newly diagnosed with diabetes in the months after infection than those without COVID-19 and those who had other respiratory infections before the pandemic. A 51-year-old Japanese woman developed acute-onset type 1 diabetes with diabetic ketoacidosis six weeks after receiving the first dose of a COVID-19 messenger ribonucleic acid (mRNA) vaccine. Laboratory tests indicated exhaustion of endogenous insulin secretion, a positive result for insulin autoantibody, and latent thyroid autoimmunity. The inhibition of mPTP opening might prevent such outcomes.
The resurgence of dormant diseases.
Mitochondria damage may be the answer to pathogens’ resurgence besides immune system exhaustion. SARS-CoV2 does decrease the body’s health. While people tend to neglect the mitochondria’s health during the viral attack and the healing process afterward, the ability of the left mitochondria to fight the dormant pathogens is reduced. There is a chance that the low level of Calcium in COVID-19 patients is because of the mPTP openings.
Most of the bacteria targeting mitochondrial morphology generally cause fragmentation of the mitochondria. Infection with L. monocytogenes leads to rapid mitochondrial fission, causing fragmentation of the mitochondrial network. H. pylori and Shigella flexneri may cause mitochondrial fragmentation. C. trachomatis induces mitochondrial elongation in the early infection process, then enhances mitochondrial fragmentation during the late phases of infection.
SARS-CoV2 is a very clever pathogen that can stimulate immune checkpoints in massive ways. Even for mild patients, the abnormality of organs still can be traced back to the mild infection. We need to understand the effectiveness of foods, herbs, and supplements in nursing our health, especially to prevent the opening of mPTP.