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Full-Text Articles in Life Sciences
9s1r Nullomer Peptide Induces Mitochondrial Pathology, Metabolic Suppression, And Enhanced Immune Cell Infiltration, In Triple-Negative Breast Cancer Mouse Model, Nilufar Ali, Cody Wolf, Swarna Kanchan, Shivakumar R. Veerabhadraiah, Laura Bond, Matthew W. Turner, Cheryl L. Jorcyk, Greg Hampikian
9s1r Nullomer Peptide Induces Mitochondrial Pathology, Metabolic Suppression, And Enhanced Immune Cell Infiltration, In Triple-Negative Breast Cancer Mouse Model, Nilufar Ali, Cody Wolf, Swarna Kanchan, Shivakumar R. Veerabhadraiah, Laura Bond, Matthew W. Turner, Cheryl L. Jorcyk, Greg Hampikian
Biology Faculty Publications and Presentations
Nullomers are the shortest strings of absent amino acid (aa) sequences in a species or group of species. Primes are those nullomers that have not been detected in the genome of any species. 9S1R is a 5-aa peptide prime sequence attached to 5-arginine aa, used to treat triple negative breast cancer (TNBC) in an in vivo mouse model. This unique peptide, administered with a trehalose carrier (9S1R-NulloPT), offers enhanced solubility and exhibits distinct anti-cancer effects against TNBC. In our study, we investigated the effect of 9S1R-NulloPT on tumor growth, metabolism, metastatic burden, tumor immune-microenvironment (TME), and transcriptome of aggressive mouse …
Mitochondrial Oma1 And Opa1 As Gatekeepers Of Organellar Structure/Function And Cellular Stress Response, Robert Gilkerson, Patrick De La Torre, Shaynah St. Vallier
Mitochondrial Oma1 And Opa1 As Gatekeepers Of Organellar Structure/Function And Cellular Stress Response, Robert Gilkerson, Patrick De La Torre, Shaynah St. Vallier
Biology Faculty Publications and Presentations
Mammalian mitochondria are emerging as a critical stress-responsive contributor to cellular life/death and developmental outcomes. Maintained as an organellar network distributed throughout the cell, mitochondria respond to cellular stimuli and stresses through highly sensitive structural dynamics, particularly in energetically demanding cell settings such as cardiac and muscle tissues. Fusion allows individual mitochondria to form an interconnected reticular network, while fission divides the network into a collection of vesicular organelles. Crucially, optic atrophy-1 (OPA1) directly links mitochondrial structure and bioenergetic function: when the transmembrane potential across the inner membrane (ΔΨm) is intact, long L-OPA1 isoforms carry out fusion of the mitochondrial …
Mitochondrial Opa1 Cleavage Is Reversibly Activated By Differentiation Of H9c2 Cardiomyoblasts, Iraselia Garcia, Fredy Calderon, Patrick De La Torre, Shaynah St. Vallier, Cristobal Rodriguez, Divya Agarwala, Megan Keniry, Wendy Innis-Whitehouse, Robert Gilkerson
Mitochondrial Opa1 Cleavage Is Reversibly Activated By Differentiation Of H9c2 Cardiomyoblasts, Iraselia Garcia, Fredy Calderon, Patrick De La Torre, Shaynah St. Vallier, Cristobal Rodriguez, Divya Agarwala, Megan Keniry, Wendy Innis-Whitehouse, Robert Gilkerson
Biology Faculty Publications and Presentations
Optic atrophy-1 (OPA1) is a dynamin-like GTPase localized to the mitochondrial inner membrane, playing key roles in inner membrane fusion and cristae maintenance. OPA1 is regulated by the mitochondrial transmembrane potential (Δψm): when Δψm is intact, long OPA1 isoforms (L-OPA1) carry out inner membrane fusion. Upon loss of Δψm, L-OPA1 isoforms are proteolytically cleaved to short (S-OPA1) isoforms by the stress-inducible OMA1 metalloprotease, causing collapse of the mitochondrial network and promoting apoptosis. Here, we show that L-OPA1 isoforms of H9c2 cardiomyoblasts are retained under loss of Δψm, despite the presence of OMA1. However, when H9c2s are differentiated to a more …
Detection Of Mitochondrial Dna (Mtdna) Mutations, Ali Naini, Robert Gilkerson, Sara Shanske, Jiuhong Pang
Detection Of Mitochondrial Dna (Mtdna) Mutations, Ali Naini, Robert Gilkerson, Sara Shanske, Jiuhong Pang
Biology Faculty Publications and Presentations
The maternally inherited mitochondrial DNA (mtDNA) is a circular 16,569-bp double stranded DNA that encodes 37 genes, twenty-four of which (2 rRNA and 22 tRNA) are necessary for transcription and translation of 13 polypeptides that are all subunits of respiratory chain. Pathogenic mutations of mtDNA cause respiratory chain dysfunction, and are the underlying defect in an ever-increasing number of mtDNA-related encephalomyopathies with distinct phenotypes. In this chapter, we present an overview of mtDNA mutations and describe the molecular techniques currently employed in our laboratory to detect two types of mtDNA mutations: Single-large scale rearrangements and point mutations.
A Disturbance In The Force: Cellular Stress Sensing By The Mitochondrial Network, Robert Gilkerson
A Disturbance In The Force: Cellular Stress Sensing By The Mitochondrial Network, Robert Gilkerson
Biology Faculty Publications and Presentations
As a highly dynamic organellar network, mitochondria are maintained as an organellar network by delicately balancing fission and fusion pathways. This homeostatic balance of organellar dynamics is increasingly revealed to play an integral role in sensing cellular stress stimuli. Mitochondrial fission/fusion balance is highly sensitive to perturbations such as loss of bioenergetic function, oxidative stress, and other stimuli, with mechanistic contribution to subsequent cell-wide cascades including inflammation, autophagy, and apoptosis. The overlapping activity with m-AAA protease 1 (OMA1) metallopeptidase, a stress-sensitive modulator of mitochondrial fusion, and dynamin-related protein 1 (DRP1), a regulator of mitochondrial fission, are key factors that shape …
The Landscape Of Mtdna Modifications In Cancer: A Tale Of Two Cities, Kate L. Hertweck, Santanu Dasgupta
The Landscape Of Mtdna Modifications In Cancer: A Tale Of Two Cities, Kate L. Hertweck, Santanu Dasgupta
Biology Faculty Publications and Presentations
Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.
Two Complete Mitochondrial Genomes From Praticolella Mexicana Perez, 2011 (Polygyridae) And Gene Order Evolution In Helicoidea (Mollusca, Gastropoda), Russell L. Minton, Marco A. Martinez Cruz, Mark L. Farman, Kathryn E. Perez
Two Complete Mitochondrial Genomes From Praticolella Mexicana Perez, 2011 (Polygyridae) And Gene Order Evolution In Helicoidea (Mollusca, Gastropoda), Russell L. Minton, Marco A. Martinez Cruz, Mark L. Farman, Kathryn E. Perez
Biology Faculty Publications and Presentations
Helicoidea is a diverse group of land snails with a global distribution. While much is known regarding the relationships of helicoid taxa, comparatively little is known about the evolution of the mitochondrial genome in the superfamily. We sequenced two complete mitochondrial genomes from Praticolella mexicana Perez, 2011 representing the first such data from the helicoid family Polygyridae, and used them in an evolutionary analysis of mitogenomic gene order. We found the mitochondrial genome of P. mexicana to be 14,008 bp in size, possessing the typical 37 metazoan genes. Multiple alternate stop codons are used, as are incomplete stop codons. Mitogenome …