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Full-Text Articles in Life Sciences

Mitochondrial Oma1 And Opa1 As Gatekeepers Of Organellar Structure/Function And Cellular Stress Response, Robert Gilkerson, Patrick De La Torre, Shaynah St. Vallier Mar 2021

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 Mar 2021

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 Jan 2020

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 Sep 2018

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 …


Oxidative Insults Disrupt Mitochondrial Dynamics, Iraselia A. Garcia Jul 2017

Oxidative Insults Disrupt Mitochondrial Dynamics, Iraselia A. Garcia

Theses and Dissertations

Mitochondria form an organellar network to provide ATP to the cell. Mitochondrial DNA (mtDNA) combines with nuclear DNA to encode polypeptides critical to forming the complexes of oxidative phosphorylation in the mitochondrial inner membrane, which generate a transmembrane potential (ΔΨm) to synthesize ATP. This ΔΨm is required to maintain mitochondria fission/fusion dynamics: organellar fusion (mediated by OPA1) and fission events (mediated by DRP1) coordinately regulate mitochondrial dynamics. While oxidative stress correlates with mitochondrial dysfunction, it is unclear how oxidants affect mitochondrial structure/function homeostasis. This project seeks to establish and examine the impact of reactive oxygen species (ROS) on mitochondrial dynamics. …


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 Jan 2016

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 …


Loss Of Mitochondrial Dna Causes Decreased Cell Viability, Alan M. Herrera Aug 2015

Loss Of Mitochondrial Dna Causes Decreased Cell Viability, Alan M. Herrera

Theses and Dissertations - UTB/UTPA

Mitochondria are an organellar network involved in cellular bioenergetics and apoptosis, and dynamically balance their organization between fusion and fission events. Mitochondrial DNA (mtDNA) and nuclear DNA combine to encode polypeptides for the complexes of oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane, which generate a transmembrane potential (ΔΨm) to synthesize ATP. Loss of ΔΨm causes mitochondrial fission, which appears to be associated with the progression of apoptosis, a critical cell death mechanism that allows tissue homeostasis, developmental sculpturing, and the removal of unwanted cells. Using cultured human cell models of decreased ΔΨm (both genetic mtDNA-depleted ρ 0 and pharmacological …