# MECHANISMS OF ORGANELLE BIOGENESIS AT THE ENDOPLASMIC RETICULUM SUBDOMAINS

> **NIH NIH R35** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2022 · $371,302

## Abstract

PROJECT SUMMARY
Intracellular membrane-bound organelles are a hallmark of all eukaryotic cells. Understanding how cells
generate different organelles remains one of the central problems in cell biology. Some organelles, like the
endoplasmic reticulum (ER) and mitochondria, are self-generating whereas other organelles can be
generated de novo. The ER plays a central role in organelle biogenesis. Even though the ER is a single
continuous membrane that extends from the outer nuclear envelope into the periphery of the cell, there are
discrete regions in the ER membrane called ER subdomains. Nascent peroxisomes and lipid droplets (LDs)
form at specialized ER subdomains. Remarkably, little is known about these ER subdomains and their role
in regulating organelle biogenesis. The goal of our research is to determine the mechanisms of peroxisome
and LD biogenesis by detailed characterization of the discrete ER subdomains using S. cerevisiae and
mammalian cell culture. Previously, we identified a family of reticulon-like ER membrane tubulating proteins,
Pex30 in yeasts and multiple C2 domains containing transmembrane proteins, MCTP1 and MCTP2, in
higher eukaryotes. We demonstrated that both Pex30 and MCTPs are localized at discrete ER subdomains
where nascent pre-peroxisomal vesicles and LDs are formed. Based on these findings, we proposed to
identify the proteins and lipids enriched at the specialized ER subdomains using unbiased as well as
candidate-based approaches. We will then test the effects of modulating the functions of candidate proteins
and lipids on the formation, abundance, morphology, and distribution of peroxisomes and LDs. Investigating
the mechanistic details of peroxisomes and LDs biogenesis from these ER subdomains is not only
important for understanding basic principles of cell biology but also has critical medical implications. Several
life-threatening neurological disorders including Zellweger syndrome associated with peroxisomal defects
and metabolic disorders such as type 2 diabetes and fatty liver disease caused due to LD defects have no
cure. Determining the mechanisms of organelle biogenesis will have implications in understanding the
pathophysiology of these disorders and provide us hints for potential therapeutic targets.

## Key facts

- **NIH application ID:** 10501463
- **Project number:** 1R35GM147189-01
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** Amit Joshi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,302
- **Award type:** 1
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501463

## Citation

> US National Institutes of Health, RePORTER application 10501463, MECHANISMS OF ORGANELLE BIOGENESIS AT THE ENDOPLASMIC RETICULUM SUBDOMAINS (1R35GM147189-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10501463. Licensed CC0.

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