Michael A Menze

University of Louisville | UL · Department of Biology

Significance Recent research has shown that intracellular proteinaceous condensates (membraneless organelles [MLOs]) are involved in various processes, ranging from Alzheimer’s disease to RNA processing, and here we demonstrate that this phenomenon governs a mechanism of anhydrobiosis. The protein Afr LEA6 is found in the desiccation-tolerant life...

To deal with increasingly severe periods of dehydration related to global climate change, it becomes increasingly important to understand the complex strategies many organisms have developed to cope with dehydration and desiccation. While it is undisputed that late embryogenesis abundant (LEA) proteins play a key role in the tolerance of plants and...

Anhydrobiotic species can survive virtually complete water loss by entering a reversible ametabolic glassy state that may persist for years in ambient conditions. The Pv11 cell line was derived from the egg mass of the anhydrobiotic midge, Polypedilum vanderplanki, and is currently the only available anhydrobiotic cell line. Our results demonstrate...

Synopsis Flight muscle histolysis is a widespread strategy used by insects to break down functional flight muscle and modulate the energetic costs associated with flight muscle use and maintenance. The variable field cricket, Gryllus lineaticeps, undergoes histolysis during their transition between dispersal flight and reproduction. Despite the imp...

MitoNEET belongs to the CDGSH Iron-Sulfur Domain (cisd)-gene family of proteins and is a [2Fe-2S] cluster-containing protein found on the outer membrane of mitochondria. The specific functions of mitoNEET/CISD1 remain to be fully elucidated, but the protein is involved in regulating mitochondrial bioenergetics in several metabolic diseases. Unfortu...

The observation that some animals can survive severe dehydration in a state approaching suspended animation (anhydrobiosis) has sparked fascination since Antony van Leeuwenhoek first described it in the early 18th century for a species of bdelloid rotifers. Centuries later, we discovered a group of intrinsically disordered polypeptides, named LEA p...

MitoNEET is a mitochondrial [2Fe-2S]-containing protein known for its involvement in cellular metabolism, iron regulation, and oxidative stress. The protein has been associated with diseases ranging from diabetes to Parkinson's disease, prompting the development of compounds designed to target mitoNEET selectively. Unfortunately, drug development i...

The proteins glutamate dehydrogenase (GDH) and mitoNEET are both targets of drug development efforts to treat metabolic disorders, cancer, and neurodegenerative diseases. However, these two proteins differ starkly in the current knowledge about ligand binding sites. MitoNEET is a [2Fe-2S]-containing protein with no obvious binding site for small li...

MitoNEET is a [2Fe-2S] redox active mitochondrial protein belonging to the CDGSH iron-sulfur domain (CISD) family of proteins. MitoNEET has been implicated as a potential target for drug development to treat various disorders, including type-2 diabetes, cancer, and Parkinson's disease. However, the specific cellular function(s) for mitoNEET still r...

Group 1 (Dur-19, PF00477, LEA_5) Late Embryogenesis Abundant (LEA) proteins are present in organisms from all three domains of life, Archaea, Bacteria, and Eukarya. Surprisingly, Artemia is the only genus known to include animals that express group 1 LEA proteins in their desiccation-tolerant life-history stages. Bioinformatics analysis of circular...

Life history and metabolism covary, but the mechanisms and individual traits responsible for these linkages remain unresolved. Dispersal capability is a critical component of life history that is constrained by metabolic capacities for energy production. Conflicting relationships between metabolism and life histories may be explained by accounting...

As global temperature shifts due to anthropogenic impacts, seasonal temperatures in shallow aquatic ecosystems are expected to increase. Previous studies on freshwater fishes that experience significant temperature changes during the annual seasons found pronounced physiological restructuring not observed in animals inhabiting more thermally stable...

Cell-based therapies have garnered significant interest to treat cancer and other diseases. Acoustofluidic technologies are in development to improve cell therapy manufacturing by facilitating rapid molecular delivery across the plasma membrane via ultrasound and microbubbles (MBs). In this study, a three-dimensional (3D) printed acoustofluidic dev...

No PDF available ABSTRACT T-cell therapies are rapidly emerging for treatment of cancer and other diseases but are limited by inefficient non-viral delivery methods. Acoustofluidic devices are in development to enhance non-viral delivery to cells. The effect of acoustofluidic parameters, such as channel geometry, on molecular loading in human T cel...

Efficient intracellular delivery of biomolecules is required for a broad range of biomedical research and cell-based therapeutic applications. Ultrasound-mediated sonoporation is an emerging technique for rapid intracellular delivery of biomolecules. Sonoporation occurs when cavitation of gas-filled microbubbles forms transient pores in nearby cell...

Tumor cell proliferation requires sufficient metabolic flux through the pentose phosphate pathway to meet the demand for biosynthetic precursors and to increase protection against oxidative stress which in turn requires an upregulation of substrate flow through glycolysis. This metabolic poise is often coupled with a shift in ATP production from mi...

Despite recent advances in biostabilization, clinical blood supplies still experience shortages and storage limitations for red blood cells (RBCs) have not yet been sufficiently addressed. Storing RBCs in a frozen or dried state is an appealing solution to address storage limitations, but many promising cryoprotectants, including the non-reducing s...

MitoNEET is a mitochondrial [2Fe‐2S] protein known for its involvement in mitochondrial bioenergetics, iron metabolism, and oxidative stress. The protein has been extensively characterized at the biochemical level since its discovery in 2004, but the mechanisms of physiological function(s) remain unresolved. Two observations seem especially relevan...

Afr LEA6 is an intrinsically disordered protein found in the anhydrobiotic cysts of Artemia franciscana . Afr LEA6 shares homology with plant seed maturation proteins (SMPs), which have been linked to the longevity of orthodox seeds in the desiccated state. Therefore, it was hypothesized that ectopically expressing Afr LEA6 will increase the desicc...

Preservation of erythrocytes in a desiccated state for storage at ambient temperature could simplify blood transfusions in austere environments, such as rural clinics, far-forward military operations, and during space travel. Currently, storage of erythrocytes is limited by a short shelf-life of 42 days at 4 °C, and long-term preservation requires...

Epigenetic mechanisms can alter gene expression and phenotypes in organisms responding to environmental changes. Within environmental parameters, temperature changes are notably the most pervasive abiotic factor for ectotherms, directly affecting organismal survival and fitness. The goal of this study was to investigate the scale of DNA methylation...

Late embryogenesis abundant (LEA) proteins are found in desiccation-tolerant species from all domains of life. Despite several decades of investigation, the molecular mechanisms by which LEA proteins confer desiccation tolerance are still unclear. In this study, dielectrophoresis (DEP) was used to determine the electrical properties of Drosophila m...

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unif...

Late embryogenesis abundant (LEA) proteins are intrinsically disordered proteins (IDPs) commonly found in anhydrobiotic organisms and are frequently correlated with desiccation tolerance. Herein we report new findings on AfrLEA6, a novel group 6 LEA protein from embryos of Artemia franciscana. Assessment of secondary structure in aqueous and dried...

Mitochondrial respiratory states and rates MitoEAGLE Task Group

MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remain...

Update of our Blood Project on WHAS11-TV https://www.whas11.com/article/news/health/method-developed-by-louisville-researchers-could-preserve-blood-for-decades/417-5d221bfc-16fe-4966-bf70-5f4eb467e262

MitoNEET is a CDGSH iron-sulfur protein which has been a target for drug development for diseases such as type-2 diabetes, cancer, and Parkinson's Disease. Functions proposed for mitoNEET are as a redox sensor and regulator of free iron in the mitochondria. We have investigated the reactivity of mitoNEET towards the reactive electrophiles 4-hydroxy...

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unif...

http://www.mitofit.org/index.php/File:Gnaiger_2019_MitoFit_Preprint_Arch_doi_10.26124_mitofit_190001.v2.pdf

The shelf-life of donated red blood cells (RBCs) for transfusions is currently limited to six weeks when stored under refrigeration. This causes supply shortages worldwide and prevents transfusions in locations that lack access to cold-chain storage. Recently, a new approach to store RBCs as a dried powder at ambient temperature was developed. This...

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unif...

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unif...

Nutrient-deprived autophagy factor 1 (NAF-1, miner1; gene cisd2) is part of the [2Fe-2S]-containing protein family which includes mitoNEET (gene cisd1) and MiNT (miner2; gene cisd3). These proteins are redox active and are thought to play an important role in cellular energy homeostasis with NAF-1 playing a critical role in calcium regulation and a...

Late Embryogenesis Abundant (LEA) proteins are a class of highly hydrophilic intrinsically disordered polypeptides (IDP) that are found in many plants and some anhydrobiotic animals. Over 15 distinct LEA proteins, belonging to three different classification groups (1,3 and 6), have been found in Artemia franciscana and several of these proteins hav...

Martinez, E., Menze, M. A., & Agosta, S. J. (2019, March). The Hungry Caterpillar: Linking Mitochondrial Energetics and Life History Traits as a Function of Temperature in Manduca sexta. In INTEGRATIVE AND COMPARATIVE BIOLOGY (Vol. 59, pp. E366-E366). JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA: OXFORD UNIV PRESS INC.

Our understanding of protein liquid-liquid phase separation (LLPS; ‘membraneless organelles’) and its importance in a wide range of biological phenomena is rapidly growing. Unexpectedly, protein LLPS may also play a role in the desiccation- and osmotic-stress tolerance of encysted Artemia franciscana (brine shrimp) embryos. AfrLEA6 is an intrinsica...

Late Embryogenesis Abundant (LEA) proteins are a remarkable group of intrinsically disordered proteins (IDPs) that confer desiccation tolerance to plants and animals that can enter a cryptobiotic state during their life cycle. AfrLEA6 contains seed maturation domains (SMD) and is expressed in the anhydrobiotic cysts of the brine shrimp Artemia fran...

Background Despite recent advances in biostabilization, clinical blood supplies still experience shortages and storage limitations for red blood cells (RBCs) have not yet been sufficiently addressed. Promising new avenues in cell stabilization include biomimetic approaches based on intracellular conditions found in animals with the ability to main...

This review compares the molecular strategies employed by anhydrobiotic invertebrates to survive extreme water stress. Intrinsically disordered proteins (IDPs) play a central role in desiccation tolerance in all species investigated. Various hypotheses about the functions of anhydrobiosis‐related intrinsically disordered (ARID) proteins, including...

Red blood cells (RBCs) must be continuously maintained at 4 °C, which poses a significant barrier to blood transfusions in far-forward locations where uninterrupted cooling is challenging. Furthermore, the maximal shelf-life of RBC transfusion units is only 42 days. The short shelf-life of transfusable units also creates a significant barrier to de...

The dimeric protein, CISD2, belongs to a unique family of [2Fe-2S] cluster containing proteins (CISD proteins), which are implicated in a variety of disorders including type-2 diabetes, Wolfram syndrome 2, and neurodegeneration. Localizing to membranes of the mitochondrion, endoplasmic reticulum, and mitochondrial-associated ER membranes, CISD2 has...

Many cell lines used in basic biological and biomedical research maintain energy homeostasis through a combination of both aerobic and anaerobic respiration. However, the extent to which both pathways contribute to the landscape of cellular energy production is consistently overlooked. Transformed cells cultured in saturating levels of glucose ofte...

Several anhydrobiotic organisms accumulate hydrophilic polypeptides, including Late Embryogenesis Abundant (LEA) proteins, before the onset of dehydration. In the brine shrimp A. franciscana, multiple LEA proteins are expressed in the desiccation tolerant life‐history stage, and these proteins localize to different subcellular compartments. The pro...

Blood transfusions are one of the most common medical procedures in hospitals, but shortages of erythrocytes often occur due to their limited shelf life (6 weeks) when refrigerated. Preservation of erythrocytes in a dried state offers a potential solution to challenges faced with blood storage, and preservative compounds such as trehalose have been...

INTRODUCTION Blood transfusions are critical life-saving medical procedures required for survival following trauma or surgery. However, red blood cells (RBCs) can only be stored for a maximum of 42 days at 4 °C, which poses a significant barrier to blood transfusions on long-term space missions. RBCs can be frozen for long-term storage, but a compl...

In order to preserve and store cells and cellular products, especially those with a short shelf-life as seen with red blood cells, cryopreservation is utilized. This method relies on dissolving the sample a cryoprotective solution, cooling the sample and storing in the vapor phase of liquid nitrogen. Researchers at U of L have developed a sonoporat...

The dimeric proteins CISD1 and CISD2 belong to a unique family of iron-sulfur cluster containing proteins and are implicated in a variety of disorders including type-2 diabetes, Wolfram syndrome 2, and neurodegeneration. Localized at the mitochondrion, endoplasmic reticulum, and mitochondria-associated ER membranes, CISD proteins are directly or in...

UofL’s Mark Hebert features our project to preserve red blood cells in a desiccated state. To access the youtube video please copy and paste the above url into your browser.

Late embryogenesis abundant (LEA) proteins are a large group of anhydrobiosis-associated intrinsically disordered proteins (IDP), which are commonly found in plants and some animals. The brine shrimp Artemiafranciscana is the only known animal that expresses LEA proteins from three, and not only one, different groups in its anhydrobiotic life stage...

The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences may occur in addition to sensitizing the cells to mitochondrial toxins. The screening of pharmaceutical agents against transformed cells while using galactose must therefore b...

Anhydrobiosis is an astounding strategy that allows certain species (both in animals and plants) to survive severe environmental conditions such as desiccation, extreme cold, or heat in the habitat. Among different molecular strategies, expression of highly hydrophilic polypeptides termed LEA proteins has been linked to the survival of plants and a...

The relationship between whole-organism growth and metabolism is generally assumed to be positive and causative; higher metabolic rates support higher growth rates. In Manduca sexta, existing data demonstrate a deviation from this simple prediction: at supraoptimal temperatures for larval growth, metabolic rate keeps increasing while growth rate is...

Cryopreservation is the only established method for long-term preservation of cells and cellular material. This technique involves preservation of cells and cellular components in the presence of cryoprotective agents (CPAs) at liquid nitrogen temperatures (-196 °C). The organic solvent dimethyl sulfoxide (Me2SO) is one of the most commonly utilize...

Abstract of the thesis & poster

A simple method to cryopreserve adherent monolayers of neuronal cells is currently not available, but the development of this technique could facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. However, complex tissues of some exceptional animals survive freezing in nature. These anima...

Main conclusion We have evaluated the endogenous expression and molecular properties of selected Group 3 LEA proteins from Artemia franciscana , and the capacity of selected Groups 1 and 3 proteins transfected into various desiccation-sensitive cell lines to improve tolerance to drying. Organisms inhabiting both aquatic and terrestrial ecosystems...

Abstract Group 3 late embryogenesis abundant (LEA) proteins are highly hydrophilic, and their expression is associated with desiccation tolerance in both plants and animals. Here we show that two LEA proteins from embryos of Artemia franciscana, AfrLEA2 and AfrLEA3m, are intrinsically disordered in solution but upon desiccation gain secondary struc...

A simple method to cryogenically preserve hepatocyte monolayers is currently not available but such a technique would facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. We investigated the effect of trehalose and dimethyl sulfoxide (Me2SO) in cryopreservation of human hepatocellular c...

MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a coval...

Introduction: The ability to effectively preserve hepatocyte monolayers in microtiter plates (MTPs) at cryogenic temperatures could greatly facilitate cell based applications in drug discovery, cell line development, and bioartifical liver support systems [1]. Even though cryogenic storage of suspended cells is a routine technique in biomedical lab...