Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types.
Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types.
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DOI：
10.1038/s41598-023-43963-5
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发表时间：
2023-10-05
影响因子：
4.6
通讯作者：
Fisher-Wellman, Kelsey H.
中科院分区：
文献类型：
--
作者：
Boykov, Ilya N.;Montgomery, McLane M.;Hagen, James T.;Aruleba, Raphael T.;McLaughlin, Kelsey L.;Coalson, Hannah S.;Nelson, Margaret A.;Pereyra, Andrea S.;Ellis, Jessica M.;Zeczycki, Tonya N.;Vohra, Nasreen A.;Tan, Su-Fern;Cabot, Myles C.;Fisher-Wellman, Kelsey H.
靶向线粒体氧化磷酸化（OXPHOS）以治疗癌症由于可能由不能区分非癌性和癌性线粒体引起的严重副作用而受到阻碍。在本文中，利用全面的线粒体表型来定义OXPHOS在各种鼠癌症中的组成和功能，并与匹配的正常组织和其他器官进行比较。当与匹配的正常组织以及高度OXPHOS依赖性器官如心脏相比时，发现OXPHOS复合物的内在表达以及OXPHOS通量在不同的癌症类型中始终较低。假设内在OXPHOS表达/功能预测体内OXPHOS依赖性，这些数据表明线粒体OXPHOS的药理学阻断可能在以临床上有意义的方式影响肿瘤线粒体通量之前损害健康氧化器官中的生物能量稳态。尽管这些数据警告不要使用不加选择的线粒体抑制剂进行癌症治疗，但在线粒体蛋白质组组成和底物特异性通量方面，在癌症类型中观察到相当大的异质性，突出了靶向特定癌症类型特有的离散线粒体蛋白或途径的可能性。
Targeting mitochondrial oxidative phosphorylation (OXPHOS) to treat cancer has been hampered due to serious side-effects potentially arising from the inability to discriminate between non-cancerous and cancerous mitochondria. Herein, comprehensive mitochondrial phenotyping was leveraged to define both the composition and function of OXPHOS across various murine cancers and compared to both matched normal tissues and other organs. When compared to both matched normal tissues, as well as high OXPHOS reliant organs like heart, intrinsic expression of the OXPHOS complexes, as well as OXPHOS flux were discovered to be consistently lower across distinct cancer types. Assuming intrinsic OXPHOS expression/function predicts OXPHOS reliance in vivo, these data suggest that pharmacologic blockade of mitochondrial OXPHOS likely compromises bioenergetic homeostasis in healthy oxidative organs prior to impacting tumor mitochondrial flux in a clinically meaningful way. Although these data caution against the use of indiscriminate mitochondrial inhibitors for cancer treatment, considerable heterogeneity was observed across cancer types with respect to both mitochondrial proteome composition and substrate-specific flux, highlighting the possibility for targeting discrete mitochondrial proteins or pathways unique to a given cancer type.
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鞘脂组成和线粒体生物能的改变代表与白血病中多药耐药性相关的协同治疗脆弱性。
DOI：
10.1096/fj.202101194rrr
发表时间：
2022-01
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
--
作者：
Lesack K;Naugler C
通讯作者：
Naugler C
影响因子：
14.9
作者：
Deutsch EW;Csordas A;Sun Z;Jarnuczak A;Perez-Riverol Y;Ternent T;Campbell DS;Bernal-Llinares M;Okuda S;Kawano S;Moritz RL;Carver JJ;Wang M;Ishihama Y;Bandeira N;Hermjakob H;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
2.9
作者：
Glancy, Brian;Willis, Wayne T.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
哺乳动物线粒体蛋白质组的组织异质性
影响因子：
5.5
作者：
Johnson, D. Thor;Harris, Robert A.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.