# Tubular lysosomes in health and disease

> **NIH NIH R35** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2022 · $354,944

## Abstract

Abstract
Age-dependent degenerative diseases, such as ALS, Alzheimer’s and Parkinson’s disease, are reaching
epidemic proportions and no viable treatment options exist to halt or reverse the course of the disease. The
lack of disease-modifying treatments is in large part due to our lack of knowledge about the molecular disease
pathology. An early hallmark of most degenerative diseases is an accumulation of protein aggregates and
damaged organelles, implying that proteostasis defects are an underlying molecular cause of degeneration.
Lysosomes are digestive organelles that clear damaged proteins and are also critical regulators of cellular
metabolism. Thus, it is not surprising that lysosome impairment is linked to a broad spectrum of degenerative
and metabolic diseases. Revealing novel ways to improve or maintain lysosome function in various biological
contexts could open promising therapeutic avenues to treat a wide range of metabolic and degenerative
diseases. We recently discovered a unique class of degradative tubular lysosomes (TLs) that are conserved in
flies, worms and mammals. Significantly, mutation of two genes required for TL maintenance are linked with
human degenerative diseases, underscoring the potential biomedical relevance of TLs. Our recent work has
demonstrated that TLs are exceptionally digestive, tissue specific and in some cases even stimulus dependent.
For example, TLs are stimulated in gut cells during starvation, a major cue that stimulates the autophagy-
lysosome system to increase nutrient recycling. We hypothesize that TLs might be deployed under certain
conditions when autophagic demand is high. This context dependency also suggests that TLs have the
capacity to be stimulated and opens the possibility that TLs could be induced in other tissues where they do
not exist naturally, such as neurons. Using worm and fly model systems, we aim to understand fundamental
aspects of TL biology in health animals and their connection to human degenerative diseases. Three major
research questions we are tackling in my lab include: (1) what are the control mechanisms for starvation-
induced TLs in the gut? (2) are TLs functionally distinct from vesicular lysosomes? and (3) is TL dysfunction an
underlying cause for age-dependent degenerative diseases? We anticipate that these studies will reveal novel
aspects of lysosome biology and might inform strategies to co-opt these mechanisms to boost lysosome
function in healthy animals or repair lysosomes in disease states.

## Key facts

- **NIH application ID:** 10456328
- **Project number:** 5R35GM138116-03
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Alyssa Johnson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $354,944
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456328

## Citation

> US National Institutes of Health, RePORTER application 10456328, Tubular lysosomes in health and disease (5R35GM138116-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456328. Licensed CC0.

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