Mitochondria are metabolic signaling centers that “influence an organism’s physiology by regulating communication between cells and tissues.” (2). Mitochondria regulate apoptosis – programmed cell death, as well as autophagy – the breakdown of cellular components during times of starvation. Mitochondria also play key roles in cellular processes including “calcium, copper and iron homeostatis; heme and iron-sulfer cluster assembly; synthesis of pyrimidines and steroids; thermogenesis and fever response; and calcium signaling” (3)
Are you confused? Do the above paragraphs sound like scientific gibberish to you leaving you wondering, “Yes, but what does that MEAN??”
The Importance of Mitochondria
Basically, it, along with the pages of information that I left out, means that mitochondria are really important to cellular functioning and health. They regulate energy production, aging, epigenetic signaling between and within cells and many other important functions. Proper functioning of mitochondria is vital, and when mitochondria are not operating properly, a wide range of disease states can ensue (2). It makes sense that if the energy centers of cells are not operating properly; the system (the body) starts to shut down in a variety of ways. “Mitochondrial dysfunction is associated with an increasingly large proportion of human inherited disorders and is implicated in common diseases, such as neurodegenerative disorders, cardiomyopathies, metabolic syndrome, cancer, and obesity.” (2) Additionally, there is significant evidence that many of the mysterious diseases of modernity, such as fibromyalgia, chronic fatigue syndrome / myalgic encephalomyelitis, Gulf War Syndrome, autism and many other chronic, multi-symptom illnesses, have their roots in mitochondrial dysfunction and resultant oxidative stress. (4)
The History of Mitochondria
The existence of mitochondria was discovered in the late 1800s. Their purpose was unknown until the 1950s when “it was first established that mitochondria are the seat of power in cells, generating almost all our energy.” (Lane p. 6) In 1967 Lynn Margulis proved the “existence of DNA and RNA in mitochondria.” (Lane p. 15) From 1967 through 1999, according to Immo Scheffler, “’Molecular biologists may have ignored mitochondria because they did not immediately recognize the far-reaching implications and applications of the discovery of the mitochondrial genes. It took time to accumulate a database of sufficient scope and content to address many challenging questions related to anthropology,biogenesis, disease, evolution, and more.’” (Lane p. 7) Almost everything that is known about the role of mitochondria in cellular signaling and gene expression (5), apoptosis, autophagy, metal metabolism, regulation of enzymes, and many other important functions, has been discovered since the turn of the century. Despite the fact that all eukaryotic organisms have (or at least once had) mitochondria, the realization that mitochondrial health is vital to over-all human health is a recent realization. The link between mitochondrial dysfunction and disease, especially chronic multi-symptom disease, is well documented in peer-reviewed journals, yet it is not an officially recognized cause of those diseases and they are considered by many to be mysterious.
Vulnerable yet Strong: Mitochondria and Tolerance Thresholds
The role of mitochondrial dysfunction in disease remains unacknowledged because of some fascinating features of mitochondria. Mitochondria are an interesting mix of vulnerable and resilient. Mitochondrial DNA (mtDNA) and mitochondrial genes are more vulnerable than nuclear DNA and nuclear genes to damage caused by chemical toxicants (like pharmaceuticals and environmental pollutants) because mitochondrial genes “sit on a single circular chromosome (unlike the linear chromosomes of the nucleus) and are ‘naked’ – they’re not wrapped up in histone proteins.” (Lane p. 15) Histone proteins protect nuclear DNA and because mtDNA isn’t wrapped in histone proteins, it is vulnerable. This vulnerability means that mtDNA is easily damaged. This slide describes additional factors that affect mitochondrial vulnerability to environmental pollutants:
Despite its vulnerability, mtDNA is, at the same time, quite hearty and resilient. MtDNA can take a punch, and a threshold of damage must be crossed over before a disease state will ensue. In Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria it is noted that, “damage to mitochondria often reflects successive chemical insults, such that no immediate cause for functional changes or pathological alterations can be established. There is indeed experimental evidence that prolonged injury to mitochondria, such as that which typifies oxidative injury to mitochondrial DNA or to components of the electron transport chain (ETC), has to cross a certain threshold (or a number of thresholds) before cell damage or cell death becomes manifest.” The researchers go on to note that, “This non-linear response can be explained upon consideration that the molecules that subserve mitochondrial function (e.g., mitochondrial DNA, mRNA, and ETC proteins) are present in excess of amounts required for normal cell function. This reserve (or buffering) capacity acts as a protective mechanism; however, at a certain stage of damage, the supply of biomolecules needed to support wild-type mitochondrial function becomes compromised.” (6)
Pharmaceutical Safety and Mitochondria: No Testing Required
To put it simply, because of the tolerance threshold that mitochondria have to damage, the damage done to mitochondria will not show up as a disease until the threshold is crossed. This makes the testing of the deleterious effects of pharmaceuticals and environmental toxins on mitochondria difficult. The damage done by the chemical toxin doesn’t show up until multiple exposures to mitochondrial damaging toxins have been experienced (and it likely doesn’t need to be the same toxin – different mitochondrial damaging toxins can erode the mitochondria’s tolerance threshold). Also, mitochondria display an “initial adaptive response was followed by a toxic response” (6) to damaging toxins.
The mitochondrial tolerance threshold for damage would need to be taken into consideration when testing drugs or environmental pollutants for their adverse effects on mitochondria, IF drugs and pollutants were tested for their effects on mitochondria at all. Unfortunately, “mitochondrial toxicity testing is still not required by the US FDA for drug approval.” (7) The authors of Mitochondria as a Target of Environmental Toxicants note that, “growing literature indicates that mitochondria are also targeted by environmental pollutants” but the EPA does not require testing of environmental pollutants for their affects on mitochondria either.
Studies have shown that bactericidal antibiotics (including fluorouquinolones) (8), statins (9), chemotherapy drugs (3), acetaminophen (6), metformin (a diabetes drug) (10), and others, damage mitochondria. The environmental pollutants that have been shown to damage mitochondria include rotenone, cyanide, lipopolysaccharide, PAH quinones, arsenic, and others (3).
Though it’s not excusable, it’s understandable that the FDA and EPA have not historically required testing of pharmaceuticals or environmental pollutants for their effects on mitochondria. Until very recently, much of what is currently known about mitochondria was not yet discovered. The link between multi-symptom chronic illnesses (including autism) and mitochondrial dysfunction and damage (4) was not yet known when the vast majority of the drugs that are on the market were going through their initial testing and review. What is known now about the important role of mitochondria in epigenetic signaling was not known until recently – and almost all laymen and probably plenty of scientists still don’t realize how much the molecules generated in our mitochondria affect our genes. All of the drugs and environmental pollutants that are on the market have been put on the market without their effects on mitochondria being studied, or even noted by the regulatory agencies that are entrusted with protecting our health and safety. The ignorance of everyone involved would be less consequential if people weren’t so sick. In addition to being connected to the mysterious diseases of modernity, mitochondrial damage is also implicated in the following disorders: “schizophrenia, bipolar disease, dementia, Alzheimer’s disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson’s disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis” (7) as well as cancer (11).
The Paradigm Shift
We’re in an interesting and strange situation where medicine hasn’t caught up to science and science hasn’t caught up to medicine. By this I mean that mitochondria damaging chemicals were created long before we knew the importance of our mitochondria, but now that scientists are realizing the importance of our mitochondria, the damaging pharmaceutical culprits are so entrenched in medicine that they can’t be extricated. For example, nalidixic acid, the precursor to fluoroquinolones (mitochondria damaging antibiotics) (8), was first created in the 1960s, long before what we currently know about mitochondria and the effects of mitochondrial damage was discovered. Now that the effects of depleting mtDNA on human health has been discovered, the myriad of strange health symptoms observed in patients who have taken fluoroquinolones can be explained. Mitochondrial damage can cause multi-symptom chronic illness (4). We know this now. However, fluoroquinolones are so widely used (20+ million annual prescriptions in America alone), and so widely regarded as safe, that it would be difficult, if not impossible, to restrict their use now – even though they have been found to cause mitochondrial damage and oxidative stress (8). It’s time for disease paradigms to shift to note the importance of mitochondria in human health. After all, chronic diseases, many of which are related to mitochondrial function, are the leading cause of death in the U.S.
Mitochondria are important. It’s time we started paying attention to them. It’s time for disease models to shift. It’s time for iatrogenic mitochondrial dysfunction to be recognized as a cause of chronic diseases. The chronic diseases are happening, whether we recognize the role of mitochondrial damage, and the role of pharmaceutical and environmental pollutants in damaging mitochondria, or not. Ignorance isn’t bliss – people are sick. With recognition of the importance of mitochondrial health, maybe we can prevent others from getting sick in the future.
Information about Fluoroquinolone Toxicity
Information about the author, and adverse reactions to fluoroquinolone antibiotics (Cipro/ciprofloxacin, Levaquin/levofloxacin, Avelox/moxifloxacin and Floxin/ofloxacin) can be found on Lisa Bloomquist’s site, www.floxiehope.com.
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Lane, Nick (2005). “Power, Sex, Suicide: Mitochondria and the Meaning of Life” Oxford University Press Inc., New York.
- Journal of Cell Biology, “Signal Transduction by Reactive Oxygen Species”
- Cell, “Mitochondria: In Sickness and in Health”
- Toxicological Sciences, “Mitochondria as a Target of Environmental Toxicants”
- Nature Preceedings, “Oxidative Stress and Mitochondrial Injury in Chronic Multisymptom Conditions: From Gulf War Illness to Autism Spectrum Disorder”
- Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms, “Mitochondrial DNA Damage and its Consequences for Mitochondrial Gene Expression”
- Molecular Interventions, “Mechanisms of Pathogenesis in Drug Hepatotoxicity Putting the Stress on Mitochondria”
- Molecular Nutrition & Food Research, “Medication-Induced Mitochondrial Damage and Disease”
- Science Translational Medicine, “Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells”
- NIH Public Access, “Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanisms”
- Biochemical Journal, “Metformin inhibits mitochondrial permeability transition and cell death: a pharmacological in vitro
- Contemporary Oncology, “Oxidative Damage and Carcinogenesis”