̽��ֱ�� of Cambridge - Trinity Hall

Throwing a ‘spanner in the works’ of our cells’ machinery could help fight cancer, fatty liver disease… and hair loss

cjb250 — Fri, 18 Apr 2025 18:00:53 +0000

Scientists at the Medical Research Council (MRC) Mitochondrial Biology Unit, ̽��ֱ�� of Cambridge, have worked out the structure of this machine and shown how it operates like the lock on a canal to transport pyruvate – a molecule generated in the body from the breakdown of sugars – into our mitochondria.

Known as the mitochondrial pyruvate carrier, this molecular machine was first proposed to exist in 1971, but it has taken until now for scientists to visualise its structure at the atomic scale using cryo-electron microscopy, a technique used to magnify an image of an object to around 165,000 times its real size. Details are published today in Science Advances.

Dr Sotiria Tavoulari, a Senior Research Associate from the ̽��ֱ�� of Cambridge, who first determined the composition of this molecular machine, said: “Sugars in our diet provide energy for our bodies to function. When they are broken down inside our cells they produce pyruvate, but to get the most out of this molecule it needs to be transferred inside the cell’s powerhouses, the mitochondria. There, it helps increase 15-fold the energy produced in the form of the cellular fuel ATP.”

Maximilian Sichrovsky, a PhD student at Hughes Hall and joint first author of the study, said: “Getting pyruvate into our mitochondria sounds straightforward, but until now we haven’t been able to understand the mechanism of how this process occurs. Using state-of-the-art cryo-electron microscopy, we’ve been able to show not only what this transporter looks like, but exactly how it works. It’s an extremely important process, and understanding it could lead to new treatments for a range of different conditions.”

Mitochondria are surrounded by two membranes. ̽��ֱ��outer one is porous, and pyruvate can easily pass through, but the inner membrane is impermeable to pyruvate. To transport pyruvate into the mitochondrion, first an outer ‘gate’ of the carrier opens, allowing pyruvate to enter the carrier. This gate then closes, and the inner gate opens, allowing the molecule to pass through into the mitochondrion.

“It works like the locks on a canal but on the molecular scale,” said Professor Edmund Kunji from the MRC Mitochondrial Biology Unit, and a Fellow at Trinity Hall, Cambridge. “There, a gate opens at one end, allowing the boat to enter. It then closes and the gate at the opposite end opens to allow the boat smooth transit through.”

Because of its central role in controlling the way mitochondria operate to produce energy, this carrier is now recognised as a promising drug target for a range of conditions, including diabetes, fatty liver disease, Parkinson’s disease, specific cancers, and even hair loss.

Pyruvate is not the only energy source available to us. Our cells can also take their energy from fats stored in the body or from amino acids in proteins. Blocking the pyruvate carrier would force the body to look elsewhere for its fuel – creating opportunities to treat a number of diseases. In fatty liver disease, for example, blocking access to pyruvate entry into mitochondria could encourage the body to use potentially dangerous fat that has been stored in liver cells.

Likewise, there are certain tumour cells that rely on pyruvate metabolism, such as in some types of prostate cancer. These cancers tend to be very ‘hungry’, producing excess pyruvate transport carriers to ensure they can feed more. Blocking the carrier could then starve these cancer cells of the energy they need to survive, killing them.

Previous studies have also suggested that inhibiting the mitochondrial pyruvate carrier may reverse hair loss. Activation of human follicle cells, which are responsible for hair growth, relies on metabolism and, in particular, the generation of lactate. When the mitochondrial pyruvate carrier is blocked from entering the mitochondria in these cells, it is instead converted to lactate.

Professor Kunji said: “Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions. Electron microscopy allows us to visualise exactly how these drugs bind inside the carrier to jam it – a spanner in the works, you could say. This creates new opportunities for structure-based drug design in order to develop better, more targeted drugs. This will be a real game changer.”

̽��ֱ��research was supported by the Medical Research Council and was a collaboration with the groups of Professors Vanessa Leone at the Medical College of Wisconsin, Lucy Forrest at the National Institutes of Health, and Jan Steyaert at the Free ̽��ֱ�� of Brussels.

Reference

Sichrovsky, M, Lacabanne, D, Ruprecht, JJ & Rana, JJ et al. Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier. Sci Adv; 18 Apr 2025; DOI: 10.1126/sciadv.adw1489

Fifty years since its discovery, scientists have finally worked out how a molecular machine found in mitochondria, the ‘powerhouses’ of our cells, allows us to make the fuel we need from sugars, a process vital to all life on Earth.

Drugs inhibiting the function of the carrier can remodel how mitochondria work, which can be beneficial in certain conditions

Edmund Kunji

bob_bosewell (Getty Images)

Bald young man, front view

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Vice-Chancellor continues UK tour

ps748 — Mon, 17 Mar 2025 14:52:55 +0000

̽��ֱ��South West of England has one of the country’s lowest levels of student progression into higher education. One of the key objectives of the visit was to engage with pupils and teachers in an area that is conspicuously under-represented in applications and admissions to Cambridge.

First stop was Colyton Grammar School, in east Devon, where Professor Prentice talked to school leaders about the barriers encountered by students from the region wishing to attend university. Joining her were representatives from Downing College, which has a particular connection to the area. They were also joined by Mike Nicholson, the ̽��ֱ��’s Director of Recruitment, Admissions and Participation, and Tom Levinson, Head of Widening Participation and Collaborative Outreach.

̽��ֱ�� ̽��ֱ�� of Cambridge and Downing College have partnered with the ̽��ֱ�� of Bristol and the Sutton Trust to support the Colyton Foundation Your Future Story – a programme that aims to support high attaining students from under-resourced backgrounds in the South West to pursue higher education opportunities.

In the evening, the Vice-Chancellor attended a reception in Bristol which was attended by nearly 50 Cambridge alumni, including one who matriculated in 1949.

̽��ֱ��following day the Vice-Chancellor travelled to North Somerset for a visit to Priory Community School, part of an Academy Trust in Worle, near Weston-super-Mare. Mike Nicholson led a school assembly for year 11 students. Later that morning, Xanthe Robertson, Access and Recruitment Officer of Trinity Hall, Cambridge, led assemblies for 1,500 students in Years 7 through to 10.

̽��ֱ��Vice-Chancellor and colleagues were interviewed by members of a student news team named after the journalist Jill Dando, who grew up in Worle. ̽��ֱ��visitors noted that among the school’s notable alumni was Stephen Jenkins, Professor of Physical and Computational Surface Chemistry at Cambridge.

̽��ֱ��next stop was Weston College, a further and higher education College in Weston-super-Mare that provides education and vocational training to students from the age of 14 through to adulthood. There the group met Sixth Form students to hear about their aspirations.

̽��ֱ��final leg of the journey took the Cambridge delegation to St Bede’s Catholic and Sixth Form College in Bristol. ̽��ֱ��school is part of the HE+ network, through which the ̽��ֱ�� of Cambridge and Colleges work together with schools FE establishments across the country to encourage applications from talented students.

Reflecting on her visit, the Vice-Chancellor said: “Travelling to the South West allowed me to learn more about the region and to understand some of the barriers to aspiration and attainment that prevent bright students from pursuing higher education. ̽��ֱ��students we met were impressive. Their teachers’ commitment to supporting their educational journey is outstanding. I hope that the outreach partnerships between the ̽��ֱ��, the Colleges and local schools will help us attract talented students to Cambridge, and will more generally encourage them to consider going to university.”

This visit to the South West followed the Vice-Chancellor’s trip to Rochdale, Manchester and Liverpool a year ago and her visit to Peterborough in the autumn of 2024.

̽��ֱ��Vice-Chancellor, Professor Deborah Prentice, has led a delegation to Devon, North Somerset and Bristol. It was the first time a serving Cambridge Vice-Chancellor had travelled to the region in an official capacity to engage with local schools and alumni.

̽��ֱ��students we met were impressive

Professor Deborah Prentice

Yes

Trump voters believe American values and prosperity are ‘under threat’

fpjl2 — Mon, 11 Nov 2024 08:31:40 +0000

Data also suggests that Democrat appeals to unity were popular across the board, but “politicians need to do more to understand why some people feel under threat”.

British Academy elects Cambridge researchers to Fellowship

ta385 — Thu, 18 Jul 2024 10:59:00 +0000

They are among 86 distinguished scholars to be elected to the fellowship in recognition of their work in fields ranging from medieval history to international relations.

̽��ֱ��Cambridge academics made Fellows of the Academy this year are:

Professor Elisabeth van Houts (History Faculty; Emmanuel College)

Professor Tim Harper (History Faculty; Magdalene College)

Professor Rosalind Love (Department of ASNC; Robinson College)

Professor James Montgomery (FAMES; Trinity Hall)

Professor Ayşe Zarakol (POLIS; Emmanuel College)

Professor Tim Dalgleish (MRC Cognition and Brain Sciences Unit)

Founded in 1902, the British Academy is the UK’s national academy for the humanities and social sciences. It is a Fellowship consisting of over 1700 of the leading minds in these subjects from the UK and overseas.

Current Fellows include the classicist Professor Dame Mary Beard, the historian Professor Sir Simon Schama and philosopher Professor Baroness Onora O’Neill, while previous Fellows include Dame Frances Yates, Sir Winston Churchill, Seamus Heaney and Beatrice Webb. ̽��ֱ��Academy is also a funder of both national and international research, as well as a forum for debate and public engagement.

In 2024, a total of 52 UK Fellows, 30 International Fellows and 4 Honorary Fellows have been elected to the British Academy Fellowship.

Professor Ayse Zarakol said: “I am absolutely delighted to be elected a Fellow of the British Academy in recognition of my interdisciplinary work at the intersection of international relations, global history and historical sociology. It is an honour to join such a long line of distinguished scholars. I very much look forward to working with the Academy to advance research on the big questions of our day and to ensure that UK remains a hospitable environment for social sciences and humanities research that attracts the best talent from around the world.”

Professor Rosalind Love said: “As a grateful recipient of one its Postdoctoral Fellowships, I have always revered the British Academy and am deeply humbled by this honour. It shows that the Academy values the teaching of Medieval Latin, and research in that area, at a time when the subject faces cuts elsewhere. I’d like to express sincerest gratitude to the teachers who gave me a solid grounding and to all who have supported me over the years: they made this possible. I look forward to working with other FBAs to shape the future of the Humanities.”

Professor Tim Harper, Head of Cambridge’s School of the Humanities and Social Sciences, said: “It is an honour to be elected a fellow of the British Academy. As a historian, I am very aware of the challenges and opportunities for the humanities and social sciences that we collectively face. I look forward to continuing to strive to strengthen their position.”

Welcoming the Fellows, President of the British Academy Professor Julia Black said: “We are delighted to welcome this year’s cohort of Fellows, and I offer my warmest congratulations to each and every one. From the Academy’s earliest days, our Fellows are the lifeblood of the organisation, representing the very best of our disciplines – and we could not do all that we do without their expertise, time and energy. I very much look forward to working closely with our new Fellows – the breadth and depth of their expertise adds so much to the Academy.”

Six academics from the ̽��ֱ�� of Cambridge have been made Fellows of the prestigious British Academy for the humanities and social sciences.

It is an honour to join such a long line of distinguished scholars.

Ayşe Zarakol

̽��ֱ��British Academy

Yes

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Hawking Archive made available to historians and researchers

zs332 — Fri, 12 Jul 2024 08:40:51 +0000

After being transferred to Cambridge by the Hawking Family in 2021, the scientific and personal archive of Professor Stephen Hawking has been fully catalogued and is now available to all who might benefit from access to it at Cambridge ̽��ֱ�� Library.

Antarctic ice shelves hold twice as much meltwater as previously thought

sc604 — Thu, 27 Jun 2024 08:56:09 +0000

Slush – water-soaked snow – makes up more than half of all meltwater on the Antarctic ice shelves during the height of summer, yet is poorly accounted for in regional climate models.

Thank you Cambridge

ps748 — Wed, 26 Jun 2024 15:03:55 +0000

Izzy Winter and Jessica (Jess) Reeve are about to embark on the next phase of their lives – entering the world of work. Izzy has just completed her Modern Languages degree (French and Italian) and Jess is finishing her Master’s in Economics. They’re excited about graduating from Cambridge but also sad they won’t be celebrating with their dear friend Clarissa Nicholls.

Moving our bodies - and mindsets

skbf2 — Fri, 07 Jun 2024 12:44:51 +0000

Moving your body and mind can help promote mental wellbeing in the workplace, say Cambridge researchers.