Mitochondria: The Future Of Medicine

MITOCHONDRIA: IMPORTANT TO PRACTICALLY EVERY DISEASE PROCESS

Pick a disease…  any disease.  Chances are, new research is linking that disease process with some aspect of Mitochondrial Dysfunction.  How can something so microscopic have such a huge impact?  Until recently, they were overlooked and their impact underestimated.  Mitochondria work within metabolic pathways that provide the abundance of energy necessary to drive every living process in the human body.  Recent research has finally begun to shift from mere evaluation of symptoms to a deeper evaluation of root-causation of those symptoms.  In doing so, Mitochondrial function continues to be implicated at an extraordinary level.  Think of Mitochondria as being responsible for a literal chain of events that support optimal health.  The disease processes that develop are now able to be traced back to the different links in the chain that became impaired or broken.  This information is now driving how researchers study disease and how they view potential new treatment and prevention methods for a majority of disease processes we face today.

Click the links below to see relevant medical journal articles and online resources that discuss the connection to Mitochondria:

MtDNA_cropAGING (yes, aging is a disease)

(2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more.

(2012) Mitochondria and aging.

(2013) The role of mitochondria in aging.

(2013) Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging.

(2014) Defects in mitochondrial DNA replication and oxidative damage in muscle of mtDNA mutator mice.

(2014) Mitochondrial Aging and Age-Related Dysfunction of Mitochondria.

(2015) Mitochondrial dysfunction in aging: Much progress but many unresolved questions.

(2016) The Mitochondrial Basis of Aging.

ALZHEIMER’S

(2010) The Alzheimer’s Disease Mitochondrial Cascade Hypothesis.

(2010) Mitochondrial dysfunction is a trigger of Alzheimer’s disease pathophysiology.

(2010) Alzheimer’s disease: diverse aspects of mitochondrial malfunctioning.

(2013) Deconstructing Mitochondrial Dysfunction in Alzheimer Disease.

(2016) Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies.

ANXIETY DISORDERS

(2005) Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders.

ARTHRITIS (Osteoarthritis)

(2013) Mitochondrial Dysfunction in Osteoarthritis Is Associated With Down-Regulation of Superoxide Dismutase 2.

AUTISM

(1998) Autism: a mitochondrial disorder?

(2008) Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment.

(2009) Evaluation and Treatment of Patients with Autism and Mitochondrial Disease.

(2010) Autism and mitochondrial disease.

(2010) Mitochondrial dysfunction in autism spectrum disorders: Cause or effect?

(2010) Mitochondrial Dysfunction in Autism.

(2011) Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders.

(2012) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis.

(2013) Autism: Metabolism, Mitochondria, and the Microbiome.

(2014) Deficits in bioenergetics and impaired immune response in granulocytes from children with autism.

(2014) Brain imaging evidence that mitochondrial dysfunction is a neurobiological subtype of Autism Spectrum Disorder.

(2014) Progressive increase in mtDNA 3243A>G heteroplasmy causes abrupt transcriptional reprogramming.

(2014) Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements.

(2015) Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder.

(2016) Mitochondrial Dysfunction in Autistic Children and Oral Coenzyme Q10 Supplementation Treatment.

(2016) Mitochondrial Dysfunction in Autism Spectrum Disorders.

(2016) Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder.

(2016) Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines.

(2016) Impaired Mitochondrial Dynamics and Mitophagy in Neuronal Models of Tuberous Sclerosis Complex.

(2017) Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder.

(2017) Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic-Based Associations, and Non-Energy-Related Mechanisms.

(2017) Next Generation Sequencing Mitochondrial DNA Analysis in Autism Spectrum Disorder.

(2017) The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder.

(2017) CLINICAL TRIAL – Mitochondrial Dysfunction in Autism Spectrum Disorder.

AUTO-INFLAMMATORY ILLNESSES (Mast Cell Activation)

(2012) Mitochondrial Components Are a Possible Trigger of Auto-inflammatory Illnesses.

BONE HEALTH

(2014) Mitochondrial Complex I Activity Suppresses Inflammation and Enhances Bone Resorption by Shifting Macrophage-Osteoclast Polarization.

CANCER

(2002) Mitochondrial defects in cancer.

(2005) Mitochondria and cancer: Warburg addressed.

(2010) The Pivotal Roles of Mitochondria in Cancer: Warburg and Beyond and Encouraging Prospects for Effective Therapies.

(2010) The Warburg effect and mitochondrial stability in cancer cells.

(2012) Mitochondrial Function and Cancer (Poster)

(2012) Mitochondria and cancer. (Douglas C. Wallace)

(2012) Warburg Effect and Mitochondrial Metabolism in Skin Cancer.

(2012) Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review).

(2012) Mitochondria and cancer: a growing role in apoptosis, cancer cell metabolism and dedifferentiation.

(2013) Mitochondria and Cancer: Past, Present, and Future.

(2013) Cancer cell metabolism: implications for therapeutic targets.

(2014) The Role of Mitochondria in Cancer and Other Chronic Diseases.

(2014) The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism.

(2015) Cancer as a mitochondrial metabolic disease.

(2015) Targeting mitochondria metabolism for cancer therapy.

(2015) Why cancer cells have a more hyperpolarised mitochondrial membrane potential and emergent prospects for therapy.

(2016) Targeting Cancer Metabolism – Revisiting the Warburg Effects.

(2016) The Warburg Effect: How Does it Benefit Cancer Cells?

(2016) Mitochondria and Cancer. (Wei-Xing Zong, Joshua D. Rabinowitz, Eileen White)

(2016) The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.

(2016) Mitochondria, cholesterol and cancer cell metabolism.

(2017) Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells.

CELIAC with NEUROLOGIC IMPAIRMENT

(2007) Sera of patients with celiac disease and neurologic disorders evoke a mitochondrial-dependent apoptosis in vitro.

CHRONIC FATIGUE SYNDROME (ME/CFS)

(2009) Chronic fatigue syndrome and mitochondrial dysfunction.

(2016) Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome.

CONNECTIVE TISSUE DISORDERS (EB, EDS, Marfan, LDS, OI)

About Mitochondrial Disorders (Connective Tissue Disorders Resource Page)

CROHN’S / ULCERATIVE COLITIS / IBS

Impaired Mitochondria and IBS/Crohn’s Ulcerative Colitis (Resource Page)

CYSTIC FIBROSIS

(2009) Dysfunction of mitochondria Ca2+ uptake in cystic fibrosis airway epithelial cells.

DEPRESSION and other MOOD DISORDERS

(2008) Mitochondrial involvement in psychiatric disorders.

(2012) Psychiatric symptoms correlate with metabolic indices in the hippocampus and cingulate in patients with mitochondrial disorders.

(2012) Impaired mitochondrial function in psychiatric disorders.

(2012) The psychiatric manifestations of mitochondrial disorders: a case and review of the literature.

(2013) Mitochondrial Functions in Mood Disorders (online resource)

DIABETES

(2010) Role of Mitochondrial Dysfunction in Insulin Resistance.

(2010) Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities.

(2012) Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus.

(2012) Mitochondria Function in Diabetes – From Health to Pathology – New Perspectives for Treatment of Diabetes-Driven Disorders.

(2015) Mitochondrial dysfunction and insulin resistance: an update.

DYSAUTONOMIA (Autonomic Dysfunction)

Dysautonomia / Autonomic Dysfunction

DYSKINESIA

(2009) Paroxysmal non-kinesigenic dyskinesia is caused by mutations of the MR-1 mitochondrial targeting sequence.

(2010) Mitochondrial Abnormalities in the Putamen in Parkinson’s Disease Dyskinesia.

(2015) Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and sensorial deficiencies, and mitochondrial complex I instability.

ECLAMPSIA  PRE-ECLAMPSIA

(1989) Pre-eclampsia–a mitochondrial disease?

(1998) Placental mitochondria as a source of oxidative stress in pre-eclampsia.

(2013) Comparative Proteomics Analysis Suggests that Placental Mitochondria are Involved in the Development of Pre-Eclampsia.

(2016) Mitochondrial [dys]function; culprit in pre-eclampsia?

(2016) Mitochondrial role in adaptive response to stress conditions in preeclampsia.

EOSINOPHILIC ESOPHAGITIS

(2009) Biology and Treatment of Eosinophilic Esophagitis

EPILEPSY

(2012) Mitochondrial disease and epilepsy.

(2015) Metabolic and mitochondrial disorders associated with epilepsy in children with autism spectrum disorder.

FIBROMYALGIA

(2004) Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle fibres.

GASTROINTESTINAL DISORDERS (general)

(2013) Unexplained gastrointestinal symptoms: Think mitochondrial disease.

HAIR DISORDERS (See also Skin Disorders below)

(2010) Aging Hair. (Senescent Alopecia)

(2015) The regulation of mitochondrial function in dermal papilla cells and the evaluation of hydrolyzed yeast extract.

(2016) Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration.

(2016) DHEA and frontal fibrosing alopecia: molecular and physiopathological mechanisms.

HEART DISEASE

(2005) Mitochondrial dysfunction in cardiovascular disease.

(2007) Mitochondrial dysfunction in atherosclerosis.

(2008) Heart mitochondria: gates of life and death.

(2009) Mitochondria in the human heart.

(2012) Mitochondria and heart disease.

(2013) Mitochondria as a therapeutic target in heart failure.

(2013) Mitochondria in heart failure: the emerging role of mitochondrial dynamics.

(2013) Mitochondrial dysfunction in heart failure.

(2015) Mitochondria, Metabolism and Heart Failure (Keystone Symposia on Molecular and Cellular Biology).

IMMUNE HEALTH (Innate and Adaptive)

(2015) Mitochondria in the regulation of innate and adaptive immunity.

INTERSTITIAL CYSTITIS / PAINFUL BLADDER SYNDROME

(2012) Protein expression profiling in interstitial cystitis/painful bladder syndrome: A pilot study of proteins associated with inflammation, apoptosis, and angiogenesis. (Connection to P53 and Mitochondrial Dysfunction as associated with IC/PBS.)

LIPOMATOSIS (Multiple Symmetrical Lipomatosis / Lipomas)

(2002) Lipoma and Sensory Neuropathy in Mitochondrial Diabetes Associated With tRNA Mutation at Position 3271.

(2004) Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation.

(2013) Multiple Symmetrical Lipomatosis–a mitochondrial disorder of brown fat.

LIVER ISSUES (Hep B, Hep C, Primary Biliary Cirrhosis, Autoimmune Hepatitis)

(2006) Mitochondrial dysfunction in hepatitis C virus infection.

(2008) Hepatitis B Virus HBx Protein Localizes to Mitochondria in Primary Rat Hepatocytes and Modulates Mitochondrial Membrane Potential.

(2013) Interactions Between Hepatitis C Virus and Mitochondria: Impact on Pathogenesis and Innate Immunity.

(2013) Hepatitis C Virus-Induced Mitochondrial Dysfunctions.

(2013) Hepatitis B Virus Disrupts Mitochondrial Dynamics: Induces Fission and Mitophagy to Attenuate Apoptosis.

(2014) Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence.

(2015) Hepatitis C Virus Attenuates Mitochondrial Lipid β-Oxidation by Downregulating Mitochondrial Trifunctional-Protein Expression.

(2015) Anti-mitochondrial M2 antibody-positive autoimmune hepatitis.

LUPUS

(2002) Mitochondrial Hyperpolarization and ATP Depletion in Patients With Systemic Lupus Erythematosus.

(2004) Mitochondrial hyperpolarization: a checkpoint of T-cell life, death and autoimmunity.

(2012) Assessment of mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus.

(2015) Normalization of CD4+ T Cell Metabolism Reverses Lupus.

(2016) Role of altered mitochondria functions in the pathogenesis of systemic lupus erythematosus.

(2016) Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease.

(2016) Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus.

MIGRAINE

(1995) Mitochondria, magnesium and migraine.

(1996) Migraine and mitochondrial dysfunction.

(1999) Mitochondrial disease and cyclic vomiting syndrome.

(2004) Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis.

(2006) Mitochondrial dysfunction and migraine: evidence and hypotheses.

(2013) Mitochondrial dysfunction in migraine.

(2013) Studies on the Pathophysiology and Genetic Basis of Migraine.

(2015) Vitamin Supplementation as Possible Prophylactic Treatment against Migraine with Aura and Menstrual Migraine.

(2015) Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial.

MULTIPLE SCLEROSIS

(2008) Mitochondria and disease progression in multiple sclerosis.

(2012) The role of mitochondria in axonal degeneration and tissue repair in MS.

(2013) Mitochondrial dysfunction and neurodegeneration in multiple sclerosis.

(2014) The central role of mitochondria in axonal degeneration in multiple sclerosis.

(2015) Mitochondrial DNA sequence variation in multiple sclerosis.

(2017) Rab32 connects ER stress to mitochondrial defects in multiple sclerosis.

MUSCULAR DEGENERATION (Duchenne’s and Becker Type Muscular Dystrophy)

(1995) Muscular degeneration in Duchenne’s dystrophy may be caused by a mitochondrial defect.

NEUROPATHY

(2005) Mitochondrial neuropathy.

(2012) Mitochondria and peripheral neuropathies.

(2013) Peripheral neuropathy in mitochondrial disorders.

PARKINSON’S

(2012) Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences.

(2014) The centrality of mitochondria in the pathogenesis and treatment of Parkinson’s disease.

PSORIASIS

Note:  Several of these articles discuss multiple disorders, including psoriasis.

(2012) Stimulated Human Mast Cells Secrete Mitochondrial Components That Have Autocrine and Paracrine Inflammatory Actions.

(2012) Discusssion of above article at: Mitochondrial Components Are a Possible Trigger of Auto-inflammatory Illnesses.

(2014) Alterations of Mitochondrial Respiration and Complex I Activity in Mononucleate Cells from Psoriatic Patients: Possible Involvement of GRIM-19-STAT3α/β.

(2014) Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases.

(2014) Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies.

(2014) Mitochondrial dysfunction: a neglected component of skin diseases.

(2015) Oxidation reduction is a key process for successful treatment of psoriasis by narrow-band UVB phototherapy.

 

RETINAL DEGENERATION

(2015) Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light.

RHEUMATOID ARTHRITIS / PSORIATIC ARTHRITIS

(2011) The mutation of mitochondrial DNA is central to the pathogenesis of rheumatoid and psoriatic arthritis.

(2011) When should a rheumatologist suspect a mitochondrial myopathy.

SKIN DISORDERS

(1999) Hair and skin disorders as signs of mitochondrial disease.  (Hair abnormalities, rashes and pigmentation disorders, hypertrichosis, and acrocyanosis.)

(2014) Mitochondrial dysfunction: a neglected component of skin diseases.  (Hair abnormalities, rashes, pigmentation abnormalities and acrocyanosis.)

SJOGREN’S SYNDROME

(2012) Sjøgren’s syndrome-associated oxidative stress and mitochondrial dysfunction: prospects for chemoprevention trials

VITILIGO

(2003) Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients.

(2013) Vitiligo: A Possible Model of Degenerative Diseases

 

MITOCHONDRIAL SPECIFIC DISORDERS

In addition to the above disorders / diseases, traditional Mitochondrial disease processes can include anything affecting the autonomic nervous system (dysautonomia), digestive processes, cellular respiration, disorders associated with muscle function and wasting/atrophy, dysfunctions affecting proper cell function, viability, and regulation of cell death/apoptosis.

The following is a list of Mitochondrial specific disorders that continues to grow:

Alpers Disease
Barth Syndrome
Beta-oxidation Defects
Acyl-Carnitine Deficiency, Carnitine Deficiency
Creatine Deficiency Syndromes
CoEnzyme Q10 Deficiency
Deficiencies in Complex I, II, III, IV (and COX Deficiency) and V
CPEO
CPT I and II Deficiencies
KSS
Lactic Acidosis
LBSL / Leukodystrophy
LCAD
LCHAD
Leigh Disease
Luft Disease
MAD / Glutaric Aciduria Type II
MCAD
MELAS
MERRF
MIRAS
Mitochondrial Cytopathy
Mitochondrial DNA Depletion
Mitochondrial Encephalopathy
Mitochondrial Myopath
MNGIE
NARP
Pearson Syndrome
Pyruvate Carboxylase Deficiency
Pyruvate Dehydrogenase Deficiency
POLG Mutations
Respiratory Chain Disorders
SCAD
SCHAD
VLCAD

 

WHY MITOCHONDRIA ARE BEING LINKED TO SO MANY DISEASES

For complex organisms like humans, ATP-energy is the very currency of life.  Without it, we cease to exist.  Practically every physiological mechanism performed by our bodies require ATP; from cellular actions, muscular function, nerve and neuron activity and beyond.  Ineffective Mitochondrial function (referred to as Mitochondrial Dysfunction) interrupts the sufficient supply of ATP.  The devastating effects are only recently being realized.

Mitochondrial Dysfunction and other related Metabolic Dysfunctions are now being linked as a common factor in practically every disease process and the list continues to grow.  As is often the case, the true cause of a disease has rarely been understood.  But as medical research continues to seek answers past symptomatology, Mitochondria are increasingly being implicated.

Heart disease is an excellent example of how the newfound link to Mitochondria is changing the medical community.  A new field of medicine is developing called Metabolic Cardiology.  If you come to these physicians symptomatic and in crisis, they initially will likely treat you as any other Cardiologist to address your immediate issue.  However, these physicians view cardiac health as being closely related to Mitochondrial health and will have a secondary objective to address and improve overall Mitochondrial function.  In fact in adult onset heart disease, some estimates suggest that by the time a patient becomes symptomatic and seeks medical attention, they may have been suffering from Mitochondrial dysfunction for up to 10 to 15 years!

The series of processes involved in cellular respiration and ATP-production can be viewed as a literal “chain” of linked events.  As researchers look passed the symptoms and continue to trace back to the source of failure, evidence points toward one or more Mitochondrial links in the chain having been broken or impaired.  The link or links broken will determine the disease process that develops.  Of course, this can be compounded because as one link is broken, stress to the overall system occurs that can end up affecting other links, triggering additional broken links and further complications.  Although creation of reactive oxygen species (ROS), otherwise called oxidative stress, is a normal and natural effect of Mitochondrial function and metabolism, the less efficient Mitochondrial function the higher the level of ROS creation.  Reducing oxidative stress (antioxidant therapy, both in the form of antioxidant supplementation and Nrf2 gene activation to increase production of Superoxide Dismutase) has become a primary focus in mediating a majority of chronic and degenerative diseases.

This compounded effect is no more evident than in the process of aging.  The biological process of aging is now considered a disease, and the disease process is rooted in both the reduction in the overall quantity of Mitochondria within cells and the decrease in Mitochondrial functional capacity.  This new knowledge offers an explanation as to why people seem to age at differing rates; it’s all a matter of how many Mitochondria, how well they function, and how quickly they can recover from damage or effects from toxic exposures (referred to as Mitochondrial DNA Repair Rate).

But the future of medicine is looking bright.  As research is being directed toward Mitochondrial dysfunction being the source of disease, more extensive knowledge is being acquired about the complexities of these little organelle and how best we can support their health.  By improving overall numbers, functional capacity and Mitochondrial DNA Repair Rate, we are beginning to unlock the answers to true preventative medicine and the ability to address symptoms and overall disease impact on quality of life.  This will finally lead to tangible and curative remedies to all the diseases that ail us.

» What Are Mitochondria

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