First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Kazuki Ueda is a joint first author on ‘ Recruitment of Peroxin 14 to lipid droplets affects lipid storage in Drosophila’, published in JCS. Kazuki is a MSc student in the lab of Andrew Simmonds at University of Alberta, Edmonton, Canada, investigating peroxisome-independent roles of Pex proteins in regulating lipid metabolism.

Kazuki Ueda

How would you explain the main findings of your paper in lay terms?

The peroxisome is an essential chemical factory in a cell that breaks down and makes special lipids in various organs. Lipid molecules can traffic from the fat reservoir of the cell, lipid droplets (LDs), to the peroxisome through direct contact. Mutations that affect core peroxisome genes, the Peroxins (Pex), may not only lead to an absence of functional organelles, but also to a spectrum of lethal, multi-systemic diseases. One of these genes encodes Pex14, which is a relatively well-characterized peroxisome-resident protein that forms a membrane-spanning pore to import matrix enzymes. Using a fruit fly model, Drosophila melanogaster, we found a unique role for Pex14 in strongly promoting lipid storage in the late-stage larvae. When we turned to Drosophila cells, we found that Pex14 was localized to the LD surface independently of mature peroxisomes, as well as the endoplasmic reticulum or mitochondria, which has been previously shown as locations where Pex14 can accumulate in the absence of peroxisomes. I found that reducing the levels of other Pex proteins responsible for inserting Pex14 into the peroxisome membrane enhances the recruitment of Pex14 to LD surfaces. Intriguingly, we found that Pex14 can prevent access of one of the LD proteins responsible for lipolysis, a process that releases lipids from the LD core. Therefore, our work demonstrates a previously unknown, peroxisome-independent function, for Pex14 in promoting lipid storage, and this may contribute to the understanding of different spectrums of peroxisomal disorders we see in some patients.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Determining the subcellular location of Pex14 was crucial in this project considering that it could be localized to other organelles in proximity to LDs. This meant that I had to rely on a sub-diffraction imaging technique. I turned to stimulated emission depletion microscopy, and in some ways, the setup was enormously different from the confocal microscope that I regularly use. Fortunately, with the assistance of the amazing personnel at the imaging facility including the fine tuning of the depletion laser, I was able to successfully image my samples and determine independent localization of Pex14 at the LDs separate from other major organelles.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

When I observed that most Pex14 localized to the LDs in Drosophila cells with a null mutation in Pex19, I was convinced of the peroxisome-independent role of Pex14 in lipid storage. I went on to show that this enhanced Pex14 localization was achieved when its peroxisomal membrane insertion was disrupted, which similarly affects peroxisome functions, and was not due to a general peroxisome biogenesis defect.

Why did you choose Journal of Cell Science for your paper?

We chose Journal of Cell Science because it is published by The Company of Biologists, which has an excellent reputation for publishing high-quality articles. The journal also publishes many papers on peroxisome and lipid droplet research, and so we felt that our work fits the scope of this journal and appeals to the audiences in related fields.

Pex14 is strongly recruited to and surrounds the lipid droplets in Drosophila Pex19KO S2R+ cells.

Pex14 is strongly recruited to and surrounds the lipid droplets in Drosophila Pex19KO S2R+ cells.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

My current supervisor, Dr Andrew Simmonds, has almost always kept his office door open for students, so there was a chance for me to discuss my new and hot experimental results. This allowed me to formulate and organize new hypotheses and gave me a clear and focused future direction.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

A simple but an astonishing truth I was exposed to during high school is that ‘each cell that makes up your body contains the same genetic material’. This drove my curiosity into wondering how it is that each cell knows what to become. Therefore, I have pursued my post-secondary education in the cell biology program, and I initially joined a different laboratory that eventually recommended that I join Dr Andrew Simmonds' lab for a more cell biology-focused work for my undergraduate research project course. This was actually a very last-minute decision, but since then, I have been enjoying my research here and continuing my graduate studies in the same lab for several years.

Who are your role models in science? Why?

I do not have a particular role model in science but I greatly respect and appreciate scientists that made and are currently making contributions to our knowledge for the betterment of our quality of life.

What's next for you?

I am continuing my research at the current lab and hoping to graduate with a PhD. I want to perform basic research to make contributions that add to scientific knowledge whether it is in academia or industry related.

Tell us something interesting about yourself that wouldn't be on your CV

There is a side of me that loves science fiction movies, and occasionally, I like to immerse myself in a world where scientific laws don't apply!

Kazuki Ueda's contact details: Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.

E-mail: kueda@ualberta.ca

Ueda
,
K.
,
Anderson-Baron
,
M. N.
,
Haskins
,
J.
,
Hughes
,
S. C.
and
Simmonds
,
A. J.
(
2022
).
Recruitment of Peroxin 14 to lipid droplets affects lipid storage in Drosophila
.
J. Cell Sci.
135
,
jcs259092
.