scholarly journals Mitochondrial-nuclear heme trafficking is regulated by GTPases that control mitochondrial dynamics

2019 ◽  
Author(s):  
Osiris Martinez-Guzman ◽  
Jonathan V. Dietz ◽  
Iryna Bohovych ◽  
Amy E. Medlock ◽  
Oleh Khalimonchuk ◽  
...  

AbstractHeme is an essential cofactor and signaling molecule. All heme-dependent processes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins in virtually every subcellular compartment. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. To address this, we developed a pulse-chase assay in which, upon the initiation of heme synthesis, heme mobilization into the mitochondrial matrix, cytosol and nucleus is monitored using fluorescent heme sensors. Surprisingly, we found that heme trafficking to the nucleus occurs at a faster rate than to the matrix or cytosol. Further, we demonstrate that GTPases in control of mitochondrial fusion, Mgm1, and fission, Dnm1, are positive and negative regulators of mitochondrial-nuclear heme trafficking, respectively. We also find that heme controls mitochondrial network morphology. Altogether, our results indicate that mitochondrial dynamics and heme trafficking are integrally coupled.

2019 ◽  
Author(s):  
Osiris Martinez-Guzman ◽  
Mathilda M. Willoughby ◽  
Arushi Saini ◽  
Jonathan V. Dietz ◽  
Iryna Bohovych ◽  
...  

AbstractHeme is an iron-containing cofactor and signaling molecule that is essential for much of aerobic life. All heme-dependent processes in eukaryotes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins located throughout the cell. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. Herein, using genetically encoded fluorescent heme sensors, we developed a live cell assay to monitor heme distribution dynamics between the mitochondrial inner-membrane, where heme is synthesized, and the mitochondrial matrix, cytosol, and nucleus. We found that heme distribution occurs simultaneously via parallel pathways. In fact, surprisingly, we find that trafficking to the nucleus is ∼25% faster than to the cytosol or mitochondrial matrix. Moreover, we discovered that the heme biosynthetic enzyme, 5-aminolevulinic acid synthase (ALAS), and GTPases in control of the mitochondrial dynamics machinery, Mgm1 and Dnm1, and ER contact sites, Gem1, regulate the flow of heme between the mitochondria and nucleus. Altogether, our results indicate that the nucleus acquires heme faster than the cytosol or mitochondrial matrix, presumably for mitochondrial-nuclear retrograde signaling, and that GTPases that regulate mitochondrial dynamics and ER contact sites are hard-wired to cellular heme distribution systems.Summary StatementThe factors that govern the trafficking of heme, an essential but potentially cytotoxic cofactor and signaling molecule, are poorly understood. Herein, we developed a live-cell assay to monitor heme distribution kinetics and identified the first enzyme in the heme synthesis pathway and GTPases in control of mitochondrial-ER contact sites and dynamics as being critical modulators of heme trafficking.


2020 ◽  
Vol 637 ◽  
pp. 117-140 ◽  
Author(s):  
DW McGowan ◽  
ED Goldstein ◽  
ML Arimitsu ◽  
AL Deary ◽  
O Ormseth ◽  
...  

Pacific capelin Mallotus catervarius are planktivorous small pelagic fish that serve an intermediate trophic role in marine food webs. Due to the lack of a directed fishery or monitoring of capelin in the Northeast Pacific, limited information is available on their distribution and abundance, and how spatio-temporal fluctuations in capelin density affect their availability as prey. To provide information on life history, spatial patterns, and population dynamics of capelin in the Gulf of Alaska (GOA), we modeled distributions of spawning habitat and larval dispersal, and synthesized spatially indexed data from multiple independent sources from 1996 to 2016. Potential capelin spawning areas were broadly distributed across the GOA. Models of larval drift show the GOA’s advective circulation patterns disperse capelin larvae over the continental shelf and upper slope, indicating potential connections between spawning areas and observed offshore distributions that are influenced by the location and timing of spawning. Spatial overlap in composite distributions of larval and age-1+ fish was used to identify core areas where capelin consistently occur and concentrate. Capelin primarily occupy shelf waters near the Kodiak Archipelago, and are patchily distributed across the GOA shelf and inshore waters. Interannual variations in abundance along with spatio-temporal differences in density indicate that the availability of capelin to predators and monitoring surveys is highly variable in the GOA. We demonstrate that the limitations of individual data series can be compensated for by integrating multiple data sources to monitor fluctuations in distributions and abundance trends of an ecologically important species across a large marine ecosystem.


Author(s):  
Madhu Ramesh ◽  
Kolla Rajasekhar ◽  
Kavya Gupta ◽  
Vardhaman Babagond ◽  
Deepak Kumar Saini ◽  
...  

A far-red turn-on fluorescent probe (Mito-TG) with excellent biocompatibility, photostability, chemical stability targets mitochondrial matrix. The insensitivity of probe under different pH and ROS enabled tracking of mitophagy and Aβ induced mitochondrial dynamics.


Ecohydrology ◽  
2021 ◽  
Author(s):  
Qiongfang Li ◽  
Yuting Zhu ◽  
Qihui Chen ◽  
Yu Li ◽  
Jing Chen ◽  
...  

2021 ◽  
Vol 13 (9) ◽  
pp. 4926
Author(s):  
Nguyen Duc Luong ◽  
Nguyen Hoang Hiep ◽  
Thi Hieu Bui

The increasing serious droughts recently might have significant impacts on socioeconomic development in the Red River basin (RRB). This study applied the variable infiltration capacity (VIC) model to investigate spatio-temporal dynamics of soil moisture in the northeast, northwest, and Red River Delta (RRD) regions of the RRB part belongs to territory of Vietnam. The soil moisture dataset simulated for 10 years (2005–2014) was utilized to establish the soil moisture anomaly percentage index (SMAPI) for assessing intensity of agricultural drought. Soil moisture appeared to co-vary with precipitation, air temperature, evapotranspiration, and various features of land cover, topography, and soil type in three regions of the RRB. SMAPI analysis revealed that more areas in the northeast experienced severe droughts compared to those in other regions, especially in the dry season and transitional months. Meanwhile, the northwest mainly suffered from mild drought and a slightly wet condition during the dry season. Different from that, the RRD mainly had moderately to very wet conditions throughout the year. The areas of both agricultural and forested lands associated with severe drought in the dry season were larger than those in the wet season. Generally, VIC-based soil moisture approach offered a feasible solution for improving soil moisture and agricultural drought monitoring capabilities at the regional scale.


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