Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New research insights into how a group of novel organelle-based disorders affects cells


A pioneering study has shed new light on how a group of novel organelle-based disorders affect cells.

The study led by Professor Michael Schrader from the University of Exeter, and featuring an international, multi-disciplinary team of scientists, has explored on peroxisome alterations and their contribution to the disease.

These are peroxisome alterations in MFF-deficient cells.

Credit: University of Exeter

Organelles are the functional units of a cell. They perform specialised functions, and defects in their enzymes performing those functions can result in metabolic disorders.

However, organelles are not just cellular factories in a production line, but are also highly dynamic. They are able to move around in the cell to interact and cooperate with other organelles and multiply by increasing in size and then dividing to adapt their number and functions to cellular needs.

Recently, scientists have identified a new group of disorders, characterised by defects in the membrane dynamics and division of organelles rather than by loss of metabolic functions.

Those disorders are caused by mutations in genes encoding for the organelle division machinery, such as Mitochondrial fission factor (MFF) - a key component of the division machinery of two organelles, mitochondria and peroxisomes.

MFF functions as an adaptor protein to recruit a mechanochemical enzyme, Dynamin-related protein 1 (DRP1), to mitochondria and peroxisomes. This enzyme can constrict and divide membranes and is essential for membrane fission and organelle multiplication.

Defects in either MFF or DRP1 block the division of mitochondria and peroxisomes and result in highly elongated organelles unable to divide. Patients with MFF deficiency present with developmental and neurological abnormalities.

The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown.

An international, multi-disciplinary team of scientists, led by Professor Michael Schrader from the University of Exeter, has now shed light on peroxisome alterations and their contribution to the disease.

Peroxisomes fulfil important protective functions in the cell and are vital for health; they contribute to cellular lipid metabolism and redox balance, which links them to the control of energy regulation, cellular ageing and age-related disorders. They also cooperate with mitochondria in the combat of viruses and anti-viral defence. Loss of peroxisome function leads to severe developmental and neurological defects such as those seen in MFF-deficiency.

"In this study, we show that MFF-deficiency impacts on the maturation of peroxisomes. Loss of MFF function results in an altered distribution of peroxisomal proteins and causes the accumulation of extremely long pre-peroxisomal membrane structures inside the cell, which have reduced import-competency for peroxisomal enzymes," said Professor Michael Schrader.

"We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH.

"Previous studies have shown that the peroxisomes in MFF-deficiency are largely functional, leading to the general assumption that defects in peroxisomal dynamics and division results only in elongated peroxisomes, which are otherwise unaltered. We have now revealed in MFF-deficient cells that this is not the case.

"Interestingly, we observed that the highly elongated peroxisomes in MFF-deficient cells are not fully static; their dynamics can be modulated, for example through the induction of organelle degradation.

"These experiments have provided us with new insights into the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity.

"In peroxisomal disorders, we often see altered numbers, different shapes or even different distributions of peroxisomes in patient cells. We also developed a mathematical modelling approach to help understand this.

"Understanding why this happens and how to modulate peroxisome numbers or distribution can provide new possibilities to improve cell performance in those patients."

"This might also be relevant to age-related conditions like dementia, deafness and blindness, as peroxisomal dynamics are known to have important protective functions within sensory cells."

The international research team combined human cell biology (Professor Michael Schrader), clinical diagnostics (Dr Sacha Ferdinandusse, Amsterdam University Medical Centre, NL; Professor Peter Freisinger, Department of Pediatrics, Reutlingen, GER), redox biology (Professor Marc Fransen, University of Leuven, BE), neurobiology (Dr Markus Islinger, University of Heidelberg, GER) and mathematic modelling (Dr David Richards, Centre for Biomedical Modelling and Analysis, LSI, Exeter, UK) to shed further light into the physical processes disturbed in MFF-deficient cells.

People with severe peroxisomal disorders, also known as Zellweger Spectrum Disorders, often die as children or young adults, and the team cooperates with a charity called Zellweger UK to raise awareness and to support families and sufferers.


The research was supported by the Biotechnology and Biological Sciences Research Council, and the EU Marie Sklodowska-Curie Innovative Training Network PerICo.

The paper, published in the Journal Biochimica et Biophysica Acta - Molecular Cell Research, is entitled: "Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation", authored by J.B. Passmore, R.E. Carmichael, T.A. Schrader, L. F. Godinho, S. Ferdinandusse, C. Lismont, Y. Wang, C. Hacker, M. Islinger, M. Fransen, D.M. Richards, P. Freisinger, and M. Schrader. See also bio-archive.

Media Contact

Duncan Sandes


Duncan Sandes | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Protein linked to cancer acts as a viscous glue in cell division
08.07.2020 | Rensselaer Polytechnic Institute

nachricht Enzymes as double agents: new mechanism discovered in protein modification
08.07.2020 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Latest News

Shock-dissipating fractal cubes could forge high-tech armor

08.07.2020 | Materials Sciences

Scientists use nanoparticle-delivered gene therapy to inhibit blinding eye disease in rodents

08.07.2020 | Health and Medicine

'Growing' active sites on quantum dots for robust H2 photogeneration

08.07.2020 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>