A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit <a rel="external noopener" href="https://www.biorxiv.org/content/biorxiv/early/2019/04/16/610220.full.pdf">the original URL</a>. The file type is <code>application/pdf</code>.
<i title="Cold Spring Harbor Laboratory">
<span class="release-stage" >pre-print</span>
Mitochondrial transcription factor A (Tfam)-mediated mtDNA maintenance and transcription, as well as leucine-rich PPR motif-containing protein (Lrpprc)-mediated mtRNA maturation and translation are essential steps of mtDNA-encoded electron transport chain (ETC) protein expression. ETC is essential for mitochondrial thermogenesis, the process of oxygen-dependent heat production inside the mitochondria in brown adipocytes. Here we describe that Tfam or Lrpprc deficiency in brown adipocytes causes<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/610220">doi:10.1101/610220</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/pzcud66omfagnphdndkj5k7scu">fatcat:pzcud66omfagnphdndkj5k7scu</a> </span>
more »... non-synchronized ETC mRNA and protein expression (NOSEMPE) and mitochondrial ETC imbalance, ultimately abolish mitochondrial thermogenesis. However, mice with NOSEMPE in brown adipocytes are cold resistant upon an acute 4C cold challenge, because of augmented nonmitochondrial thermogenesis driven by the NOSEMPE-ATF4-proteome turnover pathway. Importantly, mice with either NOSEMPE or ATF4 overexpression in brown adipocytes are protected against high-fat-diet-induced metabolic abnormalities, indicating a positive association between nonmitochondrial thermogenesis in brown adipocytes and metabolic fitness. Thus, although brown adipocytes are defined by their unique ability to produce heat through mitochondrial respiration, our study demonstrates a novel cytosolic nonmitochondrial thermogenesis in brown adipocytes. Targeting this ATF4-dependent nonmitochondrial thermogenesis in brown adipocytes may represent a new therapeutic strategy for combating metabolic disorders.
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200325001023/https://www.biorxiv.org/content/biorxiv/early/2019/04/16/610220.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/b1/1d/b11d350705b70a4dd54f7d5debc472a3095cdac6.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/610220"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>