Biology subjects

Kidwell, C. U.

Publications and source records attributed to Kidwell, C. U..

3 recordsLinked to original sources

bioRxiv2021

Laterally transferred macrophage mitochondria acts as a signaling source promoting cancer cell proliferation

Lateral transfer of mitochondria occurs in many physiological and pathological conditions. Given that mitochondria provide essential energy for cellular activities, mitochondrial transfer is currently thought to promote the rescue of damaged cells. We report that mitochondrial transfer occurs between macrophages and breast cancer cells, leading to increased cancer cell proliferation. Unexpectedly, transferred macrophage mitochondria are dysfunctional, lacking mitochondrial membrane potential. Rather than performing essential mitochondrial activities, transferred mitochondria accumulate reactive oxygen species which activates ERK signaling, indicating that transferred mitochondria act as a signaling source that promotes cancer cell proliferation. We also demonstrate that pro-tumorigenic M2-like macrophages exhibit increased mitochondrial transfer to cancer cells. Collectively, our findings reveal how mitochondrial transfer is regulated and leads to sustained functional changes in recipient cells. One-Sentence SummaryLateral transfer of macrophage mitochondria acts as a ROS signaling source, regulating cancer cell proliferation through ERK signaling.

cancer biology↗

bioRxiv2020

Msp1/ATAD1 restores mitochondrial function in Zellweger Spectrum Disease

Peroxisomal Biogenesis Disorders (PBDs) are a class of inherited metabolic disorders with profound neurological and other phenotypes. The most severe PBDs are caused by mutations in peroxin genes, which result in nonfunctional peroxisomes typically through impaired protein import. In order to better understand the molecular causes of Zellweger Spectrum Disease (ZSD) -the most severe PBDs -, we investigated the fate of peroxisomal mRNAs and proteins in ZSD model systems. We found that loss of peroxisomal import has no effect on peroxin mRNA expression or translational efficiency. Instead, peroxin proteins--still produced at high levels-- aberrantly accumulate on the mitochondrial membrane, impairing respiration and ATP generation. Finally, we rescued mitochondrial function in fibroblasts derived from human patients with ZSD by overexpressing ATAD1, an AAA-ATPase that functions in mitochondrial quality control. These findings might provide a new focus of PBD therapies in supporting quality control pathways that protect mitochondrial function.

cell biology↗

bioRxiv2017

Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum

The basic Helix-Loop-Helix transcription factor Atoh1 is required for the specification of multiple neuron types in the mammalian hindbrain including tegmental, precerebellar output neurons and cerebellar granule neurons. How a single proneural gene specifies so many neuron types from a single progenitor zone, the upper rhombic lip (URL), is not known. Here we use the zebrafish to explore the role of atoh1 in cerebellar neurogenesis. Using transgenic reporters we show that zebrafish atoh1c-expressing cells give rise to tegmental and granule cell populations that, together with previously described atoh1a-derived neuron populations, resemble the diversity of atoh1 derivatives observed in mammals. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons in the zebrafish cerebellum. Interestingly, atoh1a and atoh1c specify non-overlapping granule populations, indicating that fish use multiple atoh1 genes to generate granule neuron diversity that is not detected in mammals. By live imaging of neurogenesis at the URL we show that atoh1c is not required for the specification of granule neuron progenitors but promotes their delamination from the URL epithelium and this process is critical for neuronal maturation. This study thus provides a better understanding of how proneural transcription factors regulate neurogenesis in the vertebrate cerebellum.\n\nSummary statementatoh1 genes specify distinct populations of tegmental and granule neurons in the zebrafish hindbrain and promote their delamination from the neuroepithelium, a process critical for neuronal maturation.

developmental biology↗