I said I’d write a post about mitochondria, so here we are.
Evolution of the cell
Back in the day when life was much simpler (before multicellular was a thing), single celled organisms like the amoeba moved about quite sluggishly because they weren’t very good at producing energy (they used an anaerobic process called glycolysis which is still used in the cytosol of your cells today but produces less that 10% of cellular energy).
The story goes (this is actually the basis of evolutionary cell biology) that one day an amoeba ate/engulfed (in pacman style) a little bacterium that was whizzing around (how it caught it is puzzling but there we are).
The little bacterium had discovered a much more efficient way of producing energy (now called oxidative phosphorylation) than the amoeba – which was why it was whizzing around in the first place – and so, instead of digesting it, the amoeba decided to keep it and help it to multiply inside it so that it could harvest some of it’s energy.
And, in time, those busy bacteria became our mitochondria, living in symbiotic harmony inside our cells and everywhere else inside our bodies, apparently.
The little power houses of our cells.
And we are discovering now that they are much more than just that!
[On a side note, chloroplasts, like mitochondria, are believed to be derived from bacteria which were good at converting sunlight into starch – aka food – and which were ingested and co-opted by single celled organisms which later evolved into multicellular plant life.]
In humans, most of our mitochondria come from our mother for the simple reason that most of Dad’s mitochondria are in the tail of the sperm, powering it, and when the head of the sperm successfully penetrates the egg the tail falls off, outside and never to be seen again.
What I didn’t know until recently though – which is obvious in hindsight – is what free agents mitochondria are inside us. I had assumed that they just lived inside our cells because that is where they reproduce/replicate. But apparently they are everywhere inside us. Indeed, they can be swapped between cells and even sent on little missions like special forces… so, for example your body will send extracellular mitochondria to the site of a wound/infection where they enter, and beef up the power of, the healing/fighting cells.
Just like “midi-chlorians” in Star Wars (may the force be with you 😁)!
Now a paper unfortunately 🙄
I think the paper is aweome and that everyone should read it.
However, it is a veritable technical word salad.
One day I might try to produce a more digestible “executive summary”, but until then here are some snippets that I originally tweeted after I had read it.
You might find them interesting.
1. They produce your sex hormones! Mitochondria, which have so far been described as the major source of cellular energy, are also the site of synthesis for all steroid hormones (Bose et al., 2002). This includes progestogens (e.g., progesterone), mineralocorticoids (e.g., aldosterone), glucocorticoids (e.g., cortisol and corticosterone), androgens (e.g., testosterone), and estrogens (e.g., estriol) (reviewed in (Midzak and Papadopoulos, 2016).
2. The circle of life! Mitochondria sustain life and enable stress adaptation. (A) Within mammalian cells, mitochondria perform exactly the opposite reaction as the plant chroloroplasts [sic – not my typo! 😁]. Powered by solar energy, plants produce oxygen and food substrates (carbohydrates, lipids), which are used within mitochondria to power oxidative phosphorylation and ATP synthesis. In this process, mitochondria release carbon dioxide (CO2) and water (H2O), the substrates required by plants, thus sustaining the cycle of life.
3. They promote survival in low-oxygen conditions.. during hypoxia, mitochondria relocate near the nucleus where they produce an oxidized environment via ROS production, and which contributes to the activation of hypoxia-inducible factor 1 α (HIF1α) (Al-Mehdi et al., 2012).
4. They can effect the way your genes work. Interestingly, metabolic intermediates that are the substrates or co-factors for epigenetic modifications are all derived from the Krebs cycle and other metabolic pathways within mitochondria (reviewed in (Matilainen et al., 2017, Gut and Verdin, 2013).
5. They run hot! In mammalian cells, where enzymatic activity of the electron transport chain complexes is maximal, mitochondria are estimated to effectively function at temperatures around 50 °C (Chretien et al., 2018).
6. They can effect your mood and behaviour. A link between mitochondrial function and social behaviors has started to emerge in recent years. Notably, an increasing number of studies are reporting mitochondrial dysfunction in Autism Spectrum Disorder (ASD) (Gu et al., 2013, Tang et al., 2013), a neurodevelopmental disorder involving core alterations in social behaviors.
Another great paper to read on mitochondria can be found here…
And finally, metformin
It would be remiss of me to write about mitochondria without mentioning metformin, the drug that opened my mitochondrial rabbit hole and set me on a path leading to a daily Goat’s Rue tea habit – described in another post here.
It turns out that metformin has quite a profound effect on your mitochondria, for example, both upregulating and downregulating mitochondrial activity depending upon concentration.
I forget which way around the concentrations are but the effect is described in this paper somewhere.
Unfortunately, the paper, entitled “Mitochondria as an important target of metformin: The mechanism of
action, toxic and side effects, and new therapeutic applications” is behind a paywall. I think I paid about US$50 to access mine.
It’s well worth a read if you have the inclination and the means, but the key takeaways for me were as follows:
- Poor mitochondrial function is associated with many diseases, including cancer. Whereas, metformin has a beneficial effect on both the maintenance and the functioning of mitochondria.
- Metformin influences (inhibits) the production of glucose in humans in such a way that it is very effective at treating Type 2 diabetes.
- As well as being bad for cancer, it also affects aging by increase longevity in worms and rats
- It might also be beneficial in the treatment of heart and neurological diseases and polycystic ovary syndrome too!
So what’s the catch? The only significant catch is that, because it diverts lactic acid/lactate away from your liver to be reprocessed, it can overload your kidneys (and cause lactic acidosis) which, instead of your liver, have to get rid of these metabolites in your urine.
That’s all I have for today. 👍