skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Transient Heat Release During Mitochondrial Proton Uncoupling
Non-shivering thermogenesis through mitochondrial proton uncoupling is one of the dominant thermoregulatory mechanisms crucial for normal cellular functions. The metabolic pathway for intracellular temperature rise has widely been considered as steady-state substrate oxidation. Here, we show that a transient proton motive force (pmf) dissipation is more dominant than steady-state substrate oxidation in stimulated thermogenesis. Using transient intracellular thermometry during stimulated proton uncoupling in neurons of Aplysia californica, we observe temperature spikes of ~7.5 K that decay over two time scales: a rapid decay of ~4.8 K over ~1 s followed by a slower decay over ~17 s. The rapid decay correlates well in time with transient electrical heating from proton transport across the mitochondrial inner membrane. Beyond ~33 s, we do not observe any heating from intracellular sources, including substrate oxidation and pmf dissipation. Our measurements demonstrate the utility of transient thermometry in better understanding the thermochemistry of mitochondrial metabolism.  more » « less
Award ID(s):
1706854
PAR ID:
10175169
Author(s) / Creator(s):
; ; ; ; ; ; ;
Date Published:
Journal Name:
Communications biology
Volume:
2
ISSN:
2399-3642
Page Range / eLocation ID:
279
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. In this study, we compared the transient self-heating behavior of a homoepitaxial β-Ga2O3 MOSFET and a GaN-on-Si HEMT using nanoparticle-assisted Raman thermometry and thermoreflectance thermal imaging. The effectiveness of bottom-side and double-side cooling schemes using a polycrystalline diamond substrate and a diamond passivation layer were studied via transient thermal modeling. Because of the low thermal diffusivity of β-Ga2O3, the use of a β-Ga2O3 composite substrate (bottom-side cooling) must be augmented by a diamond passivation layer (top-side cooling) to effectively cool the device active region under both steady-state and transient operating conditions. Without no proper cooling applied, the steady-state device-to-package thermal resistance of a homoepitaxial β-Ga2O3 MOSFET is 2.6 times higher than that for a GaN-on-Si HEMT. Replacing the substrate with polycrystalline diamond (under a 6.5 μm-thick β-Ga2O3 layer) could reduce the steady-state temperature rise by 65% compared to that for a homoepitaxial β-Ga2O3 MOSFET. However, for high frequency power switching applications beyond the ~102 kHz range, bottom-side cooling (integration with a high thermal conductivity substrate) does not improve the transient thermal response of the device. Adding a diamond passivation over layer diamond not only suppresses the steadystate temperature rise, but also drastically reduces the transient temperature rise under high frequency operating conditions. 
    more » « less
  2. null (Ed.)
    Abstract Researchers have been extensively studying wide-bandgap (WBG) semiconductor materials such as gallium nitride (GaN) with an aim to accomplish an improvement in size, weight, and power of power electronics beyond current devices based on silicon (Si). However, the increased operating power densities and reduced areal footprints of WBG device technologies result in significant levels of self-heating that can ultimately restrict device operation through performance degradation, reliability issues, and failure. Typically, self-heating in WBG devices is studied using a single measurement technique while operating the device under steady-state direct current measurement conditions. However, for switching applications, this steady-state thermal characterization may lose significance since the high power dissipation occurs during fast transient switching events. Therefore, it can be useful to probe the WBG devices under transient measurement conditions in order to better understand the thermal dynamics of these systems in practical applications. In this work, the transient thermal dynamics of an AlGaN/GaN high electron mobility transistor (HEMT) were studied using thermoreflectance thermal imaging and Raman thermometry. Also, the proper use of iterative pulsed measurement schemes such as thermoreflectance thermal imaging to determine the steady-state operating temperature of devices is discussed. These studies are followed with subsequent transient thermal characterization to accurately probe the self-heating from steady-state down to submicrosecond pulse conditions using both thermoreflectance thermal imaging and Raman thermometry with temporal resolutions down to 15 ns. 
    more » « less
  3. Microscale heating platforms capable of generating localized temperature rises can find applications in wide‐ranging areas including nanomaterials synthesis and microscale thermometry. Here, commercially available optical calibration samples called Ronchi rulings, which consist of an array of chrome lines on a float glass substrate, are demonstrated to serve as reconfigurable Joule heaters. Electrical connections are formed by wire bonding onto the chrome to Joule heat individual lines and monitor their temperature rises using electrical resistance thermometry. Tests across multiple heater lines demonstrate a negative temperature coefficient of resistance with an average value of −6.93 × 10−4 ± 8.18 × 10−5 K−1. Under Joule heating, temperature rises exceeding 100 K are measured. To characterize the temperature gradient across the chrome line and glass, a noncontact optical thermometry technique based on the temperature‐dependent luminescence of upconverting nanoparticles (UCNPs) is used, producing temperature measurements that match finite element simulations. A 1:1 area ratio between the chrome lines and glass offers a high probability of finding UCNPs across both materials. The temperature rise on chrome determined from luminescence thermometry, electrical resistance thermometry, and simulations are also consistent. Furthermore, over 50% of the peak temperature rise is maintained along the neighboring glass region. 
    more » « less
  4. Synopsis Homeothermic endotherms defend their body temperature in cold environments using a number of behavioral and physiological mechanisms. Maintaining a stable body temperature primarily requires heat production through shivering or non-shivering thermogenesis (NST). Although the use of NST is well established in mammalian systems, the mechanisms and extent to which NST is used in birds are poorly understood. In mammals, one well-characterized mechanism of NST is through uncoupling of Ca2+ transport from ATP hydrolysis by sarco/endoplasmic reticulum ATPase (SERCA) in the skeletal muscle, which generates heat and may contribute to Ca2+ signaling for fatigue resistance and mitochondrial biogenesis. Two small proteins—sarcolipin (SLN) and phospholamban (PLN)—are known to regulate SERCA in mammals, but recent work shows inconsistent responses of SLN to cold acclimation in birds. In this study, we measured SERCA uncoupling in the pectoralis flight muscle of control (18°C) and cold-acclimated (−8°C) dark-eyed juncos (Junco hyemalis) that exhibited suppressed SLN transcription in the cold. We measured SERCA activity and Ca2+ uptake rates for the first time in cold-acclimated birds and found greater SERCA uncoupling in the muscle of juncos in the cold. However, SERCA uncoupling was not related to SLN or PLN transcription or measures of mitochondrial biogenesis. Nonetheless, SERCA uncoupling reduced an individual’s risk of hypothermia in the cold. Therefore, while SERCA uncoupling in the cold could be indicative of NST, it does not appear to be mediated by known regulatory proteins in these birds. These results prompt interesting questions about the significance of SLN and PLN in birds and the role of SERCA uncoupling in response to environmental conditions. 
    more » « less
  5. Oxidative metabolism meets the majority of vertebrate energy demands through the coupling of mitochondrial respiration to ATP production (OXPHOS). In endotherms, variations in OXPHOS coupling efficiency influence metabolic thermogenesis, locomotor economy and reactive oxygen species (ROS) generation. However, the extent of these variations and their functional implications in ectotherms are less clear. We measured mitochondrial oxygen consumption, ATP production and ROS production in permeabilized skeletal muscle fibres from salamanders, frogs and lizards representing ectotherm clades with low, medium and high standard metabolic rates (SMRs), respectively. Consistent with predicted associations with SMR, lizards had the highest capacities for muscle mitochondrial ATP production, while salamanders had the lowest. Unexpectedly, corresponding rates of oxygen consumption followed an opposite trend, reflecting 8.5-fold variations in OXPHOS coupling efficiency between salamanders (the lowest) and lizards (the highest). Intrinsic proton permeability of the inner mitochondrial membrane was the primary source of OXPHOS coupling variation across species, being highest in salamanders and lowest in lizards. Basal proton leak mediated by uncoupling proteins and the adenine nucleotide translocase was only seen in lizards, where it limits mitochondrial ROS production. We infer that diverse evolutionary selection pressures drive unexpectedly wide variations in muscle OXPHOS efficiency with different functional implications across ectotherm clades. 
    more » « less