# Dynamics of Mitochondrial Inheritance in C. elegans Primordial Germ Cells

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Mitochondria are dynamic double-membraned organelles that contain an independent genome (mtDNA). Each
mitochondrial gene is essential; however, mitochondrial DNA has a substantially higher rate of mutation when
compared to the nuclear genome. As a result, mtDNA mutation is one of the most common sources of genetic
disease in humans. Nonetheless, relatively few mutations have been established in mitochondrial genomes
across generations. Genetic evidence suggests that selection against mutant mtDNAs occurs in the female
germline, however, the mechanisms by which mtDNA selection occurs remain poorly understood. The goal of
the proposed research is to advance our understanding of mitochondrial DNA inheritance by
investigating the molecular and cellular mechanisms of mitochondrial inheritance in C. elegans PGCs,
which provide an outstanding model for examining mitochondrial inheritance at cellular resolution.
During late embryogenesis, C. elegans PGCs undergo a drastic remodeling process, whereby much of their cell
mass and content is discarded. PGC remodeling occurs when PGCs form organelle-filled lobe-like protrusions,
which are cut off and digested by adjacent endodermal cells. In the process, most PGC mitochondrial mass is
lost. We have observed that mitochondria initially localize into PGC lobes, but a subset subsequently migrates
back into PGCs prior to lobe removal. These are presumably the mitochondria that are inherited. I hypothesize
that PGC lobe formation and removal is a mechanism whereby the number and/or quality of
mitochondria/mtDNAs are regulated to ensure that fit mitochondria are passed on to the next generation. I will
approach this hypothesis in two ways. First, I will empirically determine which mitochondria are inherited by
PGCs and test the hypothesis that mitochondrial fission is required for proper mitochondrial segregation in PGCs
using live imaging. (AIM1). Second, I will determine if C. elegans PGC lobe formation/removal regulates
mtDNA/mitochondrial quality during inheritance. I will test the two primary hypotheses of mtDNA selection, the
mitochondrial bottleneck and purifying selection, by quantifying mtDNA prior to and following lobe removal in
wild type and mitochondrial mutant strains respectively. Then I will test the hypothesis that mitochondrial
functionality drives mitochondrial selection in PGC lobes using conserved markers of mitochondrial health
(AIM2). Mitochondrial mutations have particularly severe effects on embryonic development and male/female
infertility resulting from spermatogenesis defects, premature aging, and developmental arrest. I anticipate that
my findings will contribute to a deeper understanding of these mechanisms, and thus, will be essential for
developing treatments of human mitochondrial disease and reproductive disorders in the future.

## Key facts

- **NIH application ID:** 10474985
- **Project number:** 5F31HD102161-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Aaron Zachary Schwartz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2020-09-16 → 2023-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474985

## Citation

> US National Institutes of Health, RePORTER application 10474985, Dynamics of Mitochondrial Inheritance in C. elegans Primordial Germ Cells (5F31HD102161-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474985. Licensed CC0.

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