Not Just the Powerhouse of the Cell

The mitochondrion is  famous – if a popular Internet meme is anything to go by – as the “powerhouse of the cell.” But is it possible that mitochondria serve a purpose outside the cell? A research group led by Alain Thierry, Director of Research at INSERM, recently published a groundbreaking paper in which they identified fully functioning cell-free mitochondria in circulating blood (1). We spoke to Thierry to find out more.

Whole, functioning mitochondria in the blood – it’s a novel concept. What inspired you to investigate it?

I initially hypothesized that there might be functional mitochondria in the blood a long time ago, when I was working at the National Cancer Institute. My research involved the development of systemic delivery systems (DNA packaging structures) to transfer genes into cells with the goal of treating pathologies like cancer. When I started to work on circulating DNA (cirDNA), the cell-free DNA that cells – especially cancer cells – release into the blood, I wanted to study not only nucleus-derived, but also mitochondria-derived cirDNA.

To find out more, we developed an ultrasensitive method to detect mitochondrial cirDNA. We studied its stability and structure and demonstrated that cirDNA was composed of the full mitochondrial genome – clear indications that cirDNA was packaged in large, stable structures. Demonstration of specific markers and mitochondrial proteins, alongside electron microscopy, definitively confirmed the presence of cell-free mitochondria in blood. We further demonstrated that at least a subset of them retain their respiration competency – a discovery whose validation took over seven years.

What might be the function of circulating mitochondria?

It’s possible that they have no function. However, it was recently shown that, under certain conditions, several types of cells release mitochondria. In a few cases, stem cells may rescue damaged cells by delivering non-damaged mitochondria to them – so circulating mitochondria may participate in intercellular communication. Alternatively, due to their ancestral bacterial nature, they may participate in the immune response.

How might your discovery help in the clinic?

It is difficult to say right now, but it is highly likely that the detection of circulating mitochondria may help in the future prognosis of some diseases (such as cancer, autoimmune diseases, or infections). However, there is still a long time to go before such testing can enter the clinic. We are still at the “pre-history” of circulating mitochondrial analysis.

In light of the discovery of circulating micro-vesicles that enable cell-to-cell communication, I believe we should design new blood processing techniques that prevent the potential transfusion of these mitochondria or microvesicles. However, because current blood processing techniques are highly efficient, we should fully validate the potential health risks of transfusing these circulating mitochondria before changing our approach.

What’s next for your research?

I am now studying cell-to-cell mitochondrial transfer and the possibility of communication between cancer cells (and from cancerous to healthy cells). In collaboration with the CHU Montpellier Hospital, I am also working in pre-implantation diagnostics for in vitro fertilization.