Selected Bibliography : Mitochondrial topics - background to "long-term" COVID-19
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Think of them as stepping stones towards our goal.
Think of them as doors opening on new perspectives.
We are again underlinong here the importance of mitochondria if you still had any doubts.
We are also bringing in a host of other topics. You may not have thought of mitochondria first, when these topics were presented in the past. Now you should.
Like the books in any library, just enough references here to come back to from time to time, and thereby avoiding 'overwhelm'.
You are permitted to recall our Questionnaire's results as you scan through these references.
If you need help with recalling these responses: Energetics.
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> Damage to mitochondrial DNA (its DNA) happens with aging. You might have guessed that.
Decline in skeletal muscle mitochondrial function
> Maternal ancestry and racial origins show differences in mitochondrial damage in blood vessel cells.
Endothelial Cell Bioenergetics and Mitochondrial DNA
> How mitochondrial functions impinge on health a disease. How will that fit into future therapies?
Mitochondria - in sickness and in health
> Mitochondria, Hydrogen peroxde (H2O2), creation & control, and use in communicating energy levels to points outsiude of the cell.
Mitochondria can act as energy-sensing regulators of hydrogen peroxide availability
> Mitochondrial energetics, and a reply to a Comment.
Mitochondria, complexity, and evolutionary deficit spending
> Mitochondrial function varies from one tissue to the next. Here adipocytes (fat cells), and a view of obesity as a probable mitochondrial disease.
Mitochondrial (Dys)function in Adipocyte (De)differentiation and Systemic Metabolic Alterations
> A related and critical observation on mitochondria and fat cells. Recall the fat gain is frequently seen in "long-term" COVID-19 patients. Adipocytes (fat cells) are behaving quite unexpectedly. We have other articles on this, but here's a part of that puzzle.
Mitochondrial Complex III ROS Regulate Adipocyte Differentiation
> While our principle topic is not cancer, here is a study showing differences in racial groups' incidence of prostate cancer, as clearly linked to racial differences in populations of mitochondria. Again, as we always try to work our way back to the "long-term" COVID-19 population and the sample that we studied, racial differences there fit very nicely with this study.
Mitochondrial dysfunction and prostate cancer racial disparities among American men
The article summarizes these findings with this graphic, bringing many findings together.
Undesired changes and overall reduction in mitochondrial DNA leads to disease.
> Substrates fro mitochondrial work, what we feed them essentially, will create markedly different outputs of reactive oxygen species (consider these bad, but that's simplified). But signaling functions from mitochondria can be greatly influenced by substrate differences.
Sites of reactive oxygen species generation by mitochondria oxidizing different substrates
> The DNA of mitochondria, their genome, as with other chromosomes and genes of the nucleus, are susceptible to damage. Repair is essential if normal function is to continue. Some repair happens through communication with outside cellular organelles charged with repair. Some repair is internal to the mitochondrion. This article emphasizes its essential role. Illnesses that affect repair mechanisms, have serious censequences.
Mitochondrial Genome Maintenance: Damage and Repair Pathways
Mitochondria & GENDER Differences
> Here we start with the basics: mice. But the results are still interesting as one begins to think about mitochondrial gender differences. "Here, we examine if sex disparity in mitochondria
function, morphology, and redox status starts early and hence can be implicated in sexual dimorphism in cardiac as well as neurological disorders prevalent at young age. Although mitochondrial activity in the heart did not significantly vary between sexes, female brain exhibited enhanced respiration
and higher reserve capacity."
Sex‐specific differences in mitochondria biogenesis, morphology, respiratory function
> Still with the mice. Still intresting. "These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function."
> Ah ... Humans? No, not yet. Still mice. Paraoxanase 2 differences in male and female brains.
"These results suggest that PON2 is a novel major intracellular factor that protects
CNS cells against oxidative stress, and confers gender-dependent susceptibility to such stress. The
lower expression of PON2 in males may have broad ramifications for susceptibility to diseases
involving oxidative stress, including neurodegenerative diseases." Recall that Parkinson's disease in humans, is almost exclusively a male disease. So this is an example of how basic research is pushing our understanding of mitochondria and their many fundtions besides ATP creation, far ahead at almost the speed of light.
GENDER DIFFERENCES IN BRAIN SUSCEPTIBILITY TO Oxidative stress
> Humans? Nope. Mice. Males have impaired cardiac energy function and signaling events. Sound like a problem related to outcomes for men in an ICU setting? (Humans in ICU, not mice). Yes, potentially.
Obesity, diabetes, cardiovascular function. We found at least 2 of those in our questionnaire responses.
Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse
> Ah, humans. Gotta love 'em.
Our questionnaire confirmed that those with "long-term" COVID-19 who present with this disease, were just over 90% female. And in that sample, a gender comparison revealed some important diferences in how the illness manifests. In this article below, we find anew, differences related to mitochondria. These are not just in one organ or tissue. Here, both blood cells and brain show gender-specific differences.
> Differences in mitochondrial respiration parameters in men and women (humans). Superios intrinsic mitochondrial respiration in women. (Again, think of men having respiratory difficulties in an ICU setting).
"These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise."
Superior Intrinsic Mitochondrial Respiration in Women Than in Men
> Human : The one you've been looking for. Excellent work.
"It appears that mitochondria are the place of marked sexual dimorphism involving mainly oxidative capacities, calcium handling, and resistance to oxidative stress. In turn, sex hormones regulate mitochondrial function and biogenesis. ... Sex differences in the occurrence, development, and outcome of pathologies become more and more obvious. Yet, the consideration of sex differences in clinical and experimental research is still poorly acknowledged. Pathologies with a better prognosis in women involve protective effects of estrogens and mitochondria. Pathologies with a female disadvantage like autoimmune disorders seem to be less dependent on mitochondrial dysfunction as a primary factor. "
Mitochondria - a central target for sex differences in pathologies
Comment: Given all of the above findings pertaining to gender diferences and mitochondrial function, there is every reason to believe that the findings that emerge from responses to the questionnaire, and related specifically to energetics, fit right in to the topic headlined here.
Mitochondria & Mental Health
> What happens when mitochondria are placed under stress?
Mitochondria May Hold Keys to Anxiety and Mental Health
> An introduction to "mitochondrial allostatic load" (MAL) - maladaptive mitochondrial adjustments to stress do occur.
Psychological Stress and Mitochondria - A Systematic Review
> Psychologic stress induces structural and functional recalibration of mitochondria - a role in psychosomatic illnesses due to MAL.
Psychological Stress and Mitochondria - A Conceptual Framework
> Mitochondrial psychobiology: an emerging field
Mitochondrial psychobiology - foundations and applications
> The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations and their signalling of sources of stress present in our environment.
Mitochondrial Stress Signaling Promotes Cellular Adaptations
> Faulty mitochondria can both directly and indirectly promote inflammation.
Mitochondrial Nexus To Allostatic Load Biomarkers
> Neurodegenerative diseases are incurable and inexorably progressive conditions that affect
the central nervous system and result in a selective pattern of neuronal death. A plethora of reports indicate that mitochondrial dysfunction is a central factor in the pathophysiology of neurodegenerative diseases. This review is quite complete.
Mitochodrial Dysfuncion & Neurodegeneration
> Four main elements connect mitochondria to stress: (1) Energy is required at the molecular, (epi)genetic, cellular, organellar, and systemic levels to sustain components of stress responses;
(2) Glucocorticoids and other steroid hormones are produced and metabolized by mitochondria;
(3) Reciprocally, mitochondria respond to neuroendocrine and metabolic stress mediators; and
(4) Experimentally manipulating mitochondrial functions alters physiological and behavioral responses to psychological stress
An energetic view of stress - Focus on mitochondria
> Chronic stress may induce recalibrations in mitochondria leading to changes either in mitochondrial content per cell, or in mitochondrial functional capacity (i.e., quality).
A Mitochondrial Health Index Sensitive to Mood and Caregiving Stress
> Mitochondrial myopathy can lead to respiratory problems that require support from a ventilator.
Clearly a topic pertinent to COVID-19 illness when more severe. Not a consequence that this figures so prominently in our respondent's comments about how they breathe. The article below comes from the literature on maternally inherited mitochondrial diseases. The title speaks to myophathies. The main symptoms of mitochondrial myopathy are muscle weakness and wasting, and exercise intolerance. The links to our respondents appears once again.
Facts About Mitochondrial myopathies
And below, normal mitochondrion structure/ function and abnormal findings in mitochondrion in Depression and sites of antidepressant medication actions.
Mitochondria, gathered together to communicate change in their environment ...
Mental Health & COVID-19
> This doesn't pertain to "long-term" COVID-19 but to reports on the mental health consequences. The take away point is that caution is to be applied when drawing conclusions without appropriate controls. We heartily agree.
Caution when linking COVID-19 to mental health consequences
> "... we should adopt an active stance, both in outpatient and in inpatient settings. As in other fields of outpatient medicine, our focus should shift from elective to emergency consultations. Psychiatrists with currently less workload in elective care should reach out to colleagues working in emergency settings. In outpatient clinics, we should actively engage in teleconsultations, using webcams to facilitate observation." Very consistent with our findings relating to effective sources of emotional support.
Psychiatry in the times of Coronavirus Disease - Time to act now
> When its time to give it a break ... " As people are repeatedly exposed, through personal experiences and media consumption, to anxiety-provoking topics related to this growing health crisis, it is vital
for health professionals, researchers, and policy makers to be able to recognize the clinical signs of dysfunctional thought processes related to the COVID-19 crisis."
How much “Thinking” about COVID-19 is clinically dysfunctional
> "When it comes to psychological problems, prevention and early identification exceed treatment."
We heartily agree. And our questionnaire's results attest to the fact that this was generally not an effective solution for emotional support in our respondents. It should be.
Depression and anxiety among adolescents during COVID-19 - A cross-sectional study.
> And now, a disturbing problem that our questionnaire's responses alerted us to: Suicidal Ideation and Suicide Risk.
"Exacerbated physical health problems could increase risk for some patients, especially among older adults, in whom health problems are associated with suicide. One patient illustrated the psychological toll of COVID-19 symptoms when he told his clinician, “'I feel like (you) sent me home to die."
The title of this article can not be bettered.
Psychiatry in the times of Coronavirus Disease - Time to act now.
> "COVID-19 presents a new and urgent opportunity to focus political will, federal investments, and global community on the vital imperative of suicide prevention. Suicide prevention in the COVID-19 era requires addressing not only pandemic-specific suicide risk factors, but also prepandemic risk factors."
Suicide Prevention in the COVID-19 Era
END of this Bibliography for now
- We will likely add more pertinent references in the near future
- I notice that this is a relatively short bibliography. Most of the articles that I have published in the past, had much more significant collections of topic-related references.
- Volume is not the goal here. instead, providing an initial awareness of probable links between findings in our sample of respondents, and everything mitochondria: that's the goal. We could have focused on everything related to respiratory symptoms as discovered by the questionnaire. (Q. 29 for example). And actually, those are very likely mitochondrial in origin as well.
So balancing background with "getting to the point," does not need an overly long bibliography.
We are trying to make this as effective and convincing a journey as we can, while still keeping the overload as minimal as possible.
Doing it otherwise, and just blurting out the end of the story, would lack a foundation that makes that ending believable.
But we do want to keep it simple. Like an old fashioned duck shoot at a fair.
But even there, one had to go through the right steps to hit the target.
Next, we'll get much closer >>>>>>>
Shifting the focus of answers to our questionnaire: Energetics
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A découvrir aussi
- Mitochondria : Amazing, and simply Amazing !
- Mitochondria : Get sick sometimes
- Mitochondria & COVID-19 : stepping stones from the "peer-reviewed" literature