Mitochondria and Us: from exploration to global collective

Mitochondria are the sites in our cells responsible for making the energy needed to sustain life. They are involved not only in controlling the function of cells, but also in determining how cells die. Mitochondrial dysfunction underpins diseases like cancer, neurodegeneration and diabetes, and primary mitochondrial diseases are complex, incurable and often misdiagnosed. Mitochondrial research has provided seminal discoveries that span decades and have had broad ramifications for cellular health. Recent examples include advances in precise editing of the mitochondrial DNA, the important role of mitochondrial dynamics and modifications of internal mitochondrial architecture, the roles of mitochondria in signalling processes, the emerging role of mitochondria in infection and immunity and the malleability of mitochondrial biogenesis and links to cellular metabolism in response to stress. Many of these advances have resulted from an astute interdisciplinary approach, involving chemistry, physics and data science and applying these to fundamental questions of mitochondrial biology with a view to provide therapeutic advances in mitochondrial medicine. This is an exciting time for mitochondrial research, spanning all aspects of how mitochondria are made, how they sustain life, how they underpin disease and how they control cell death. This research is impactful, international and highly interdisciplinary. This article reflects on a journey that explored this potential in creative and ambitious ways.

In summer 2019, the Innovation School (IS) at the Glasgow School of Art (GSA) was invited by the Biochemical Society (BS) to organize a 1-day interdisciplinary workshop between BS members close to or local to Glasgow and design researchers at the GSA. Elio Caccavale (Reader in Transdisciplinary Design Innovation, IS GSA) and Dr Michael Pierre Johnson (Creative Economy Leadership Fellow, IS GSA) were responsible for developing and delivering the workshop at GSA on 7 November 2019. The workshop was attended by 16 participants, including design researchers and practitioners from GSA and biochemical scientists from the University of Glasgow (UofG), the University of Strathclyde (UofS) and Glasgow Caledonian University (GCU).

The event was titled ‘Crossover’ and explored the potential for exchanges between design and biochemical sciences. Specifically, it focused on sharing disciplinary expertise and perspectives to explore research opportunities for collaborative science and society projects. The workshop also provided the scope to initiate design and science dialogues to bring tangible form to the abstract and complex contributions of scientific research and its social implications (Figure 1).

The Crossover workshop aimed to act on clear motivations to communicate biochemical sciences in creative and engaging ways and to join up traditionally siloed scientific, policy, critical, communication and creative disciplines in ways that could stimulate new collaborations, new inquiries and innovative outcomes and reach new audiences. There was a clear sense from everyone involved that this type of initiative should happen again, so we explored opportunities for further transdisciplinary partnerships.

Professor Kostas Tokatlidis (Cathcart Chair of Biochemistry and Head of the Mitochondrial Biology Lab at the UofG) was one of the participants in the workshop and showcased the mitochondrial research (and applications to mitochondrial medicine) as a key area where such cross-over approaches can be pioneered to create new and impactful ways of engagement and innovative narratives to reach wider audiences. The critical and innovative concept brought to the foreground was to develop research in a mitochondria-centric, disease-agnostic manner, by bringing mitochondria to the centre of medical research, transcending traditional disease-siloed approaches and going beyond the links to primary mitochondrial disease by exploring further the connection of mitochondrial dysfunction to common human disorders that affect millions (cancer, cardiometabolic disease and neurodegeneration). Towards this goal the University of Glasgow mitochondrial integrative research network aims to develop new cross-cutting research and novel tools, collaborate nationally and internationally to drive disruptive progress in fundamental mitochondrial mechanisms, diagnostics, precision mitochondrial delivery and therapeutic approaches together with the pharma industry, policy changes and in outreach/education. Amongst the many ideas discussed, three fundamental questions emerged for further exploration in the context of mitochondrial research and societal engagement:

• What do we know and still need to learn about mitochondria and how we as researchers in the field communicate scientific advances?

• What effects do mitochondrial dysfunction and disease have on people’s lives?

• Who should we bring together to understand this and what it means for society?

Follow-on discussions led professor Kostas Tokatlidis to organize an international online event for Mitochondrial Disease Awareness Week (13–19 September 2020) together with Elio Caccavale and Dr Michael Pierre Johnson and with the support of the Royal Society of Edinburgh (RSE) who embraced this as part of the RSE’s societal engagement and outreach activities.

The aim of the event was to co-curate a cross-over of interdisciplinary expertise, practice and personal experiences exploring the impact of mitochondrial research and related disorders on society. Mitochondria and Us: Interdisciplinary Stories from Science and Society on the Powerhouse CEO of the Cell highlighted stories from across scientific disciplines that shed light on how mitochondria are made, how they sustain cell life under stress and how they control cell death. The event was based on contributions from world experts of a variety of scientific disciplines that are integral to mitochondrial research (biology, chemistry, physics, data science and medicine). Importantly, it also brought together patient groups, the ‘women in mitochondria’ research group, social scientists, bioethicists and designers to share stories of what the understanding of mitochondria means for people and society. This online webinar was also part of the RSE Regional Champions event and was run in partnership with the UofG, the GSA and the Lily Foundation (the largest UK mito patient charity organization). It had a very wide reach with an attendance of over 350 people from all continents across the world.

Consecutively in 2021, the Biochemical Society, with the support of Dr Pedro Ferreira (Education, Public Engagement and Training Manager), sponsored a new-phase Crossover Project, co-funded by the RSE Young Academy of Scotland (YAS). The Crossover Project aimed to build further a network of interdisciplinary exchange between science, society and design to develop transdisciplinary practices that creatively address complex challenges and opportunities that arise with the advancement of scientific knowledge and technology. To do this, the Crossover Project hosted a new series of three workshop programmes, with more focused contexts related to understanding and caring for invisible diseases and community STEM education.

The first of these workshops, Mitochondria and Us: Co-creating Science and Society Narratives of Mitochondrial Disease (Figure 2), built on partnership with professor Kostas Tokatlidis, took place online over Zoom and Miro on 25 February 2021. The workshop brought together 14 participants from a unique variety of expertise across biochemistry, design, social sciences and humanities to co-create stories that could support greater understanding of people’s experiences living with and working with mitochondrial diseases. Participants shared their perspectives through discussions and reflections across societal, experiential and biochemical levels (Figure 3) to co-create opportunities for collaboration across multiple disciplines that could challenge the current disease-siloed approach and build stronger connections across research, clinicians and patients.

With the momentum from these discussions, we were introduced to professor Ana Andreazza (Thomas C. Zachos Chair in Mitochondrial Research, University of Toronto) and Sonya Brijbassi (Associate Director, Strategy & Partnership for Mitochondrial Innovation Initiative (MITO2i)); at the University of Toronto, who had also been pioneering engaging forms of collaboration across research, industry and patient groups.

Mitochondrial dysfunction has a direct impact on patients’ lives. In 2014, a mother to a living son with bipolar disorder (and two deceased children with mitochondrial disease) participated in a webinar discussing mitochondrial dysfunction in relation to bipolar disorder; afterward, she contacted professor Andreazza to ask if these two diseases were linked and, if so, how. Enquiries like these, and growing support in the literature, led to the creation of MITO2i – a network of researchers, clinicians, patient advocates and partners with a mission to transform our understanding of the role of mitochondria in human health and disease. Researchers and medical professionals recognize that mitochondrial dysfunction plays a significant role in common, chronic diseases, including neurodevelopmental, neuropsychiatric, neurodegenerative disorders and multiple metabolic disorders. MITO2i’s vision is to innovate mitochondrial medicine and research through global community building, interdisciplinary research and development of novel tools and platforms. MITO2i’s goal is to transform the understanding of mitochondrial health and disease, leading to better diagnoses and treatments that enhance the quality of human life, ultimately transforming healthcare by integrating mitochondrial health into routine care. The relationship between mitochondrial dysfunction and severe mitochondrial disease has long been known. More recent research has established links to a broad range of neurodegenerative and metabolic disorders. This is a game-changer. Unveiling how mitochondrial dysfunction is implicated in multiple diseases will transform medical diagnoses, technologies and drug delivery systems, leading to a paradigm shift in the prevention, diagnosis and treatment of disease. MITO2i is delivering a collaborative hub that engages all stakeholders in advancing science in the field of mitochondrial medicine and research and engaging in global collaborative efforts like the one developed with UofG and GSA.

In our discussions, the idea of forming a Global Mito Collective emerged to provide a mito-centric approach to bridge new collaborations that can help build a new understanding on the role mitochondria play in our lives. An essential aspect identified for such a collective was to empower scientific collaboration across mitochondrial research disciplines, by generating an interdisciplinary ‘collective’ of international scientists, social scientists, bioethicists, patient groups, clinical groups and design researchers that seek to contribute to the understanding and caring for mitochondrial diseases and dysfunctions using innovative approaches.

We co-developed and co-presented a proposal for the Global Mito Collective, first as an online panel discussion with mitochondrial disease foundations at the World Mitochondrial Disease Awareness Week 2021 programmed in partnership with the Biochemical Society and organized by professor Kostas Tokatlidis, professor Ana Andreazza, Sonya Brijbassi, Dr Michael Pierre Johnson and Elio Caccavale and facilitated by Gaston Welisch (Research Associate, IS GSA). This was followed by a second discussion at the Mito2021 Conference organized and co-hosted by MITO2i, MitoCanada and the Brain and Mind Institute at the University of Ottawa .

Both events enabled discussion and input on what such a Global Mito Collective should do (Figure 4), as well as what the benefits could be, building towards a series of aims that could shape forms of collaboration and value creation moving forward.

MITO RESEARCH – for a shared understanding of cell health

MITO VOICES – to share experiences of those affected by or working with mitochondria

MITO COURSES – to develop skills in research and clinical impact

MITO MEDICINE – as part of everyday treatment and advice

MITO MATTERS – for collective dialogue on the urgent matters for development

Steps have since taken place to contribute to focused developmental discussions with diseases foundations, mitochondrial research centres, industry and healthcare stakeholders, with a view to present and launch a developed proposal for the Global Mito Collective during the World Mitochondrial Disease Week 2022.

Globally, there are many excellent research centres with their own focus on some aspects of mitochondrial research and with their own expertise, often built over many years of frontier research achievements. Some examples in the UK are the MRC Mitochondrial Biology Unit and the Wellcome Trust Mitochondrial Research Centre as well as centres in Oxford and London. Relevant networks include the North American Disease consortium, the Mitochondrial Medicine Society and several patient advocate groups and charities like the Lily foundation and MyMitoMission in the UK, the United Mitochondrial Disease Foundation (UMDF) in the USA and several other foundations across the world (some with broader remits like Alzheimer’s and Parkinson’s disease foundations). Funding organizations supporting high-risk, high-reward projects to a better society and improve the field of medicine (Michael J Fox Foundation, Bill & Melinda Gates Foundation and others) have funded and can play a critical role in supporting highly innovative mitochondrial research, which also has the potential to attract eventually investment from pharma to develop new therapeutics that target mitochondrial function.

While all of the above is critical to obtain an in-depth understanding of specific human diseases and mitochondrial dysfunctions, there is increasing awareness that expanded collaborations are critical to develop a more holistic, mitochondria-focused, but disease-agnostic approach to mitochondria research. This is an ambitious vision, but aligns well with the idea of the Mito Collective (Figure 5) along the lines we have highlighted in this article.