Mitopharmacogenomics: The Power of Mitochondria Over Your Medicine Cabinet

Did you know that your mitochondrial DNA (mtDNA) can determine which drugs heal you and which ones harm you?

MtDNA is the great forgotten player in pharmacogenetics, but it can determine why a drug that saves lives in some people becomes toxic in others!

Below you will find how small changes in this genetic code shape your response to common medications:

1. Antibiotics: Breaking the Silence

Aminoglycosides (AGs), such as gentamicin or neomycin, are antibiotics used to treat severe bacterial infections. They act by inhibiting bacterial protein synthesis through binding to the 30S ribosomal subunit. The m.1555A>G mutation, located in the 12S rRNA gene, alters the human mitochondrial ribosome, making it more similar to its bacterial counterpart and therefore susceptible to aminoglycosides. The result is a toxic side effect: ototoxicity, leading to hearing loss upon exposure to these drugs.

 

2. Anesthesia and the Metabolic “Blackout”

Volatile anesthetics and some neuromuscular blockers rely on mitochondria to sustain energy production under physiological stress. Certain mtDNA variants can increase sensitivity to volatile anesthetics, raising the risk of lactic acidosis or organ dysfunction during surgery.

 

3. Antiepileptic Drugs and Sudden Liver Failure

Valproic acid (VPA) is a widely used antiepileptic drug but has a well-known mitochondrial toxic profile, as it inhibits β-oxidation. The liver, which is highly dependent on mitochondrial function, is particularly vulnerable. Mutations in the gene encoding mitochondrial DNA polymerase (POLG) reduce mtDNA copy number, severely affecting energy-demanding tissues such as the liver and brain. In patients carrying POLG mutations, VPA can be fatal due to hepatic mitochondrial collapse.

 

4. Antiretrovirals (HIV) and Chemotherapy: The Cost of Energy

Some HIV treatments and certain chemotherapeutic agents directly impair mtDNA replication. As a consequence of mitochondrial toxicity, patients may develop extreme fatigue, muscle weakness (myopathy), and nerve damage (neuropathy). In these cases, it is not only the disease—the treatment itself contributes to the damage.

 A new organelle: Hemifusome

🧠 You know, I am a scientist and despite of having taken almost 3 week of vacation, my curious brain is always looking for interesting news related to my expertise...

During my break, I read an article about the discovery of a 𝐧𝐞𝐰 𝐨𝐫𝐠𝐚𝐧𝐞𝐥𝐥𝐞...

😱 What? ... Yes... You are reading well!

A new organelle called '𝐇𝐞𝐦𝐢𝐟𝐮𝐬𝐨𝐦𝐞'

Fascinating, isn't it?

𝐇𝐞𝐦𝐢𝐟𝐮𝐬𝐨𝐦𝐞 acts as a '𝐥𝐨𝐚𝐝𝐢𝐧𝐠 𝐝𝐨𝐜𝐤' or 𝐫𝐞𝐜𝐲𝐜𝐥𝐢𝐧𝐠 𝐜𝐞𝐧𝐭𝐞𝐫, facilitating the formation of vesicles (small transport packages) and the transfer of material within the cell. They are 𝐭𝐞𝐦𝐩𝐨𝐫𝐚𝐥 𝐬𝐭𝐫𝐮𝐜𝐭𝐮𝐫𝐞𝐬 that appear and disappear depending on cell necessities, that have been observed thanks to advanced techniques such as 𝐜𝐫𝐢𝐨𝐓𝐄𝐂 (cryogenic electron tomography).

Alterations in membrane fusion pathways involving hemifusome intermediates have been linked to:

- 𝐍𝐞𝐮𝐫𝐨𝐝𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐯𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞𝐬
- 𝐋𝐲𝐬𝐨𝐬𝐨𝐦𝐚𝐥 𝐬𝐭𝐨𝐫𝐚𝐠𝐞 𝐝𝐢𝐬𝐨𝐫𝐝𝐞𝐫𝐬
- 𝐃𝐞𝐟𝐞𝐜𝐭𝐬 𝐢𝐧 𝐞𝐧𝐝𝐨𝐬𝐨𝐦𝐚𝐥 𝐭𝐫𝐚𝐟𝐟𝐢𝐜𝐤𝐢𝐧𝐠

This finding, led by the University of Virginia and the National Institutes of Health (NIH), represents a 𝐬𝐢𝐠𝐧𝐢𝐟𝐢𝐜𝐚𝐧𝐭 𝐝𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐲 𝐢𝐧 𝐜𝐞𝐥𝐥 𝐛𝐢𝐨𝐥𝐨𝐠𝐲.

Have you heard about 'Hemifusome'?



Reference

Tavakoli, A., Hu, S., Ebrahim, S. et al. Hemifusomes and interacting proteolipid nanodroplets mediate multi-vesicular body formation. Nat Commun 16, 4609 (2025). https://lnkd.in/egMnpP69                         

𝐉𝐚𝐩𝐚𝐧 𝐥𝐨𝐧𝐠𝐞𝐯𝐢𝐭𝐲

🎎As you probably remember from other posts, I love Japanese culture and … surprisingly I love Sumo!!

🤼‍♂️Last week ‘The January Grand Sumo Tournament’ began and every night my partner, we watch the highlights of the day.

As I have a curious nature, I am not only focused on how the sumo wrestlers try to knock out each other, I observe the sumo audience. Tournament after tournament I have realized that the majority of the spectators are old, really old. So, I researched about 𝐉𝐚𝐩𝐚𝐧 𝐥𝐨𝐧𝐠𝐞𝐯𝐢𝐭𝐲 and I have discovered that it's not just genetic, it is due to a very interesting combination of factors that directly influence cellular aging:

𝟏) 𝐓𝐫𝐚𝐝𝐢𝐭𝐢𝐨𝐧𝐚𝐥 𝐉𝐚𝐩𝐚𝐧𝐞𝐬𝐞 𝐝𝐢𝐞𝐭 🥢

Rich in fish, vegetables, seaweed, and fermented foods → less inflammation and better metabolic health.

𝟐) 𝐓𝐚𝐢𝐬𝐨 𝐨𝐫 𝐂𝐨𝐧𝐬𝐭𝐚𝐧𝐭 𝐦𝐨𝐯𝐞𝐦𝐞𝐧𝐭🚶‍♀️

Physical activity integrated into daily life (not necessarily intense exercise) to improve mitochondrial function. Mainly gentle exercises for health and joints focused on range of motion.

𝟑) 𝐈𝐤𝐢𝐠𝐚𝐢 𝐨𝐫 ‘𝐀 𝐫𝐞𝐚𝐬𝐨𝐧 𝐟𝐨𝐫 𝐛𝐞𝐢𝐧𝐠’🧠

Having a reason to get up every day is associated with less stress and better mental health.

𝟒) 𝐌𝐨𝐚𝐢 𝐨𝐫 ‘𝐒𝐨𝐜𝐢𝐚𝐥 𝐜𝐨𝐧𝐧𝐞𝐜𝐭𝐢𝐨𝐧’👥

Strong social networks that act as a protective factor against accelerated aging.

🔬 At a biological level, these habits are associated with:

• Less chronic inflammation

• Improved response to oxidative stress

• Greater neuronal protection

• Healthier aging

𝐋𝐨𝐧𝐠𝐞𝐯𝐢𝐭𝐲 𝐢𝐬 𝐧𝐨𝐭 𝐣𝐮𝐬𝐭 𝐚𝐛𝐨𝐮𝐭 𝐥𝐢𝐯𝐢𝐧𝐠 𝐥𝐨𝐧𝐠𝐞𝐫, 𝐛𝐮𝐭 𝐚𝐛𝐨𝐮𝐭 𝐥𝐢𝐯𝐢𝐧𝐠 𝐛𝐞𝐭𝐭𝐞𝐫 𝐚𝐭 𝐭𝐡𝐞 𝐜𝐞𝐥𝐥𝐮𝐥𝐚𝐫 𝐥𝐞𝐯𝐞𝐥.

👌 Definitely a good 𝐈𝐊𝐈𝐀𝐆𝐈 and more 𝐌𝐎𝐀𝐈 to stay youth!

 

Did you know that there is a narrow relation between mitochondrial DNA and Parkinson’s disease?

    Mitochondria are the only organelles in the cells that contain their own genetic material (mtDNA). Specifically, human mtDNA is a double-stranded circular molecule of 16,569 base pairs that encodes 37 genes: 13 proteins essential for oxidative phosphorylation, 22 tRNAs, and 2 rRNAs. Each cell contains many mitochondria, and each mitochondrion carries multiple copies of mtDNA that varies between 5 to 10. Interestingly, mtDNA is inherited almost exclusively from the mother. Due to limited repair mechanisms and exposure to reactive oxygen species, mtDNA accumulates mutations faster than nuclear DNA. This could lead to cells containing a mixture of normal and mutated mtDNA. During human evolution, functional variants in mtDNA have been accumulated leading to the appearance of genealogical groups of mtDNA (named haplogroups) sharing a common maternal ancestor. These haplogroups are mostly separated among specific populations and geographic areas. Mutations in mtDNA are associated with mitochondrial disorders, neurodegenerative diseases, aging, and metabolic conditions. Pathological modifications in mitochondrial genome are classified in three wide groups: (1) mtDNA point mutations (inherited or somatic), (2) mtDNA deletions, and (3) alterations in the mtDNA copy number. Evidence suggests that genetic variations in mtDNA increases with age and may contribute to the pathogenesis of neurodegenerative disorders such as Alzheimer’s, Parkinson’s diseases (PD) or amyotrophic lateral sclerosis.

 Parkinson’s Disease and mtDNA

Several evidences have demonstrated that alterations in mitochondrial structures (such as mtDNA) and functions are involved in the onset and progression of neurodegenerative diseases, including Parkinson’s disease (PD). PD is the most common neurologic movement disorder affecting 2% of the population older than 60 years. Symptoms of PD include muscle rigidity, balance disturbances, and tremor. This neurodegenerative disease is characterized by progressive loss of dopaminergic neurons (DA) in substantia nigra par compacta (SNPC). DA are particularly exposed to higher levels of oxidative stress due to dopamine metabolism creating an environment favorable for alterations of mtDNA. Damage in mtDNA compromises mitochondrial bioenergetics and can lead to cell death. Which are the alterations in mtDNA associated to PD? Within the classification explained above, we can mainly find mtDNA deletions and alterations in the mtDNA copy number in a specific brain region or in a cell type-specific manner. For instance, mtDNA deletions and a reduced number in mtDNA copies are more prevalent in SNPC of patients with PD compared to patients with other movement disorders. Interestingly, in peripheral tissues (blood, muscle, fibroblasts) the results are more heterogeneous. Some studies report reduced mtDNA copy number in blood from PD patients but others find no change or even compensatory increases. Moreover, certain haplogroups have been shown to modulate susceptibility to develop PD. In European populations, haplogroups J and K are consistently associated with a reduced risk of PD, likely due to these variants promote slightly lower oxidative phosphorylation efficiency and reduced reactive oxygen species production and therefore limiting cumulative oxidative damage in DN. In contrast, some studies suggest that the haplogroup H, characterized by higher respiratory efficiency and increased oxidative stress, is associated with a modestly increased susceptibility to PD. Overall, mtDNA haplogroups act as genetic modifiers influencing in mitochondrial function and neuronal vulnerability.

 

To conclude, the scientific community has made significant advances in understanding the role of mtDNA copy numbers, haplogroups, mutations, and deletions in the physiopathology of PD and this might be considered the only neurodegenerative disease consistently associated with specific mtDNA haplogroups.

References: 

DOI: 10.1089/dna.2020.5398

 The Most Relevant Scientific Advances of 2025 

In 2025, we witnessed the consolidation of technologies that allow for an unprecedented understanding and manipulation of life. Here I show you the most influential findings in Biology, Biochemistry, and Medicine that define this year:

1. The AI-CRISPR Fusion and the Genetic Precise Edition

The CRISPR gene-editing tool has become smarter and more precise thanks to its integration with AI. AI models have been developed that predict the efficiency and potential off-target effects of CRISPR therapies. Furthermore, the significant advancement in delivering CRISPR components directly to an affected organ or tissue is maximizing the success of gene editing for rare and chronic diseases.

2. The New Horizon of Neurodegeneration

The treatment of neurodegenerative diseases is undergoing a radical shift, with new approaches that go beyond symptomatic management. In 2025, research has focused on how GLP-1 hormone analogs (originally developed for diabetes and obesity) could have significant neuroprotective effects, slowing the progression of neurodegenerative diseases such as Parkinson's. Moreover, the use of three-dimensional organoids allows for more accurate simulation of human brain pathologies, accelerating the testing of new bioactive compounds.

3. New Vaccines generation in Oncology

mRNA technology isn't limited to infectious diseases; it's driving precision medicine in oncology. This year, promising progress has been made in Phase III clinical trials for mRNA vaccines designed to instruct a patient's immune system to recognize and destroy specific tumor cells.

4. Bioengineering and Unique Materials Synthesis

Through the modification of microorganisms, synthetic biology produces complex proteins or advanced biomaterials (such as synthetic spider silk or new biopolymers) on a large scale, with applications in tissue regeneration and the creation of biodegradable packaging.

The findings from 2025 confirm that the future of medicine is precise, personalized, and proactive. The convergence of biochemistry, genetics, and AI is poised to cure what was once incurable.

From ORIGAMI to MEDICINE 

🏯 I am passionate about Japanese culture and I often watch documentaries about Japanese curiosities. Yesterday, a documentary called Origami caught my attention.

🤔 Did you know that this artistic purpose has become a fundamental source of inspiration in biomedical engineering and nanotechnology?

Origami (paper folding) has the principle of "deterministic shape change": the ability to transform from a flat, compact form into a complex, three-dimensional structure in a precise and controlled manner.

The use of origami in medicine is divided into two main areas:

🔬 1. Nano-Origami (DNA Origami)

Technique of creating nanostructures with remarkable precision using strands of DNA as building blocks. The DNA is folded into specific shapes (such as boxes, tubes, or microscopic robots).

Example of Medical Applications:
💊 Targeted Drug Delivery: Nano-origami is used to create "capsules" or "robots" that can encapsulate drugs or genetic material (such as RNA or DNA) and deliver them directly to diseased cells or tissues (e.g., cancer cells), releasing their payload only upon detecting a specific signal from the tumor.

🛠️ 2. Macro and Micro-Inspired Origami (Medical Devices)

In the field of device engineering, origami enables miniaturization and functionality in minimally invasive surgeries.

❤️ Example of Practical Applications:
Deployable Implants and Stents: Stents for expanding narrowed blood vessels (e.g., in the heart or brain) can be designed with origami-like folding patterns. This allows them to be inserted in a compressed state through a small catheter and to deploy in a predetermined way upon reaching body temperature or through mechanical activation.

In essence, origami transforms medical design, allowing biological structures and artificial devices to use form as function, opening up a vast field for smarter, safer, and less invasive therapies and surgeries.

👀 Did you know Origami has emerged as a crucial design paradigm for the future of biomedicine and nanotechnology?

Why do we yawn?

Why do we yawn?

It’s Thursday. I just had lunch. I am tired and… I can't stop yawning!!

Despite my tiredness, my brain doesn't stop and I wonder … Why do we yawn?

Interestingly, yawning is a multifactorial reflex that involves the brainstem, respiratory system and autonomic nervous system. Indeed, there is no single cause, but several mechanisms work together.

Let’s see more about yawning!

📢 Reset button: from low alertness to high alertness

 * You yawn when:

 - You’re tired

 - You’re bored

 - You’re just waking up

 - You need to stay alert

 * Yawning triggers:

 - A surge of oxygen intake

 - Increased heart rate

 - Activation of the sympathetic nervous system

🧠 Cool down the brain

 * When you yawn, you take in a deep, rapid breath of cool air.

 * This increases blood flow to the skull.

 * The stretching of jaw muscles increases vascular circulation and moves warm blood out.

 * Cooler blood then reaches the brain → brain temperature drops slightly.

 📌 A cooler brain works more efficiently, especially when transitioning between states (sleepiness ↔ alertness).

 

 

🥱 Yawning is highly contagious!

Are you the kind of person that yawns where someone does it?