Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease

被引：54

作者：

Li, Xi ^{[1
,2
,3
]}

Zhang, Yinan ^{[4
]}

Xu, Lingya ^{[5
,6
]}

Wang, Aoxue ^{[1
,2
,3
]}

Zou, Yejun ^{[1
,2
,3
]}

Li, Ting ^{[1
,2
,3
]}

Huang, Li ^{[1
]}

Chen, Weicai ^{[1
]}

Liu, Shuning ^{[1
]}

Jiang, Kun ^{[1
]}

Zhang, Xiuze ^{[1
]}

Wang, Dongmei ^{[5
,6
]}

Zhang, Lijuan ^{[1
]}

Zhang, Zhuo ^{[1
,2
,3
]}

Zhang, Zeyi ^{[1
]}

Chen, Xianjun ^{[1
,2
,3
]}

Jia, Wei ^{[4
]}

Zhao, Aihua

Yan, Xinfeng ^{[7
]}

Zhou, Haimeng ^{[8
]}

Zhu, Linyong ^{[1
]}

Ma, Xinran ^{[5
,6
]}

Ju, Zhenyu ^{[9
]}

Jia, Weiping ^{[4
]}

Wang, Congrong ^{[10
]}

Loscalzo, Joseph

Yang, Yi ^{[1
,3
]}

Zhao, Yuzheng ^{[1
,2
]}

机构：

[1] East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, State Key Lab Bioreactor Engn,Sch Pharm, 130 Mei Long Rd, Shanghai 200237, Peoples R China

[2] Chinese Acad Med Sci, Res Unit New Tech Live Cell Metab Imaging, Beijing 100730, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China

[4] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Ctr Translat Med, Metab Dis Biobank, 600 Yishan Rd, Shanghai 200233, Peoples R China

[5] East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[6] East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[7] Tongji Univ, Shanghai East Hosp, Translat Med Ctr Stem Cell Therapy, Dept Endocrinol,Sch Med, Shanghai 200120, Peoples R China

[8] Tsinghua Univ, Zhejiang Prov Key Lab Appl Enzymol, Yangtze Delta Reg Inst, Jiaxing 314006, Peoples R China

[9] Jinan Univ, Inst Aging & Regenerat Med, Guangzhou Regenerat Med & Hlth Guangdong Lab, Key Lab Regenerat Med,Minist Educ, Guangzhou 510632, Peoples R China

[10] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA

来源：

CELL METABOLISM | 2023年 / 35卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ENCODED FLUORESCENT SENSORS; ENERGY-METABOLISM; NAD(+) METABOLISM; SKELETAL-MUSCLE; LIVE CELLS; MITOCHONDRIA; HOMEOSTASIS; DIAGNOSIS; DYNAMICS; INSULIN;

D O I：

10.1016/j.cmet.2022.10.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Despite its central importance in cellular metabolism, many details remain to be determined regarding sub -cellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and charac-terize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly en-riched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.

引用

页码：200 / +

页数：22

共 65 条

[1] Aguilera L, 2008, J BACTERIOL, V190, P2997, DOI [10.1128/JB.02013-07, 10.1128/JB.00815-08]
[2] MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo
Bayraktar, Erol C.
Baudrier, Lou
Ozerdem, Ceren
Lewis, Caroline A.
Chan, Sze Ham
Kunchok, Tenzin
Abu-Remaileh, Monther
Cangelosi, Andrew L.
Sabatini, David M.
Birsoy, Kivanc
Chen, Walter W.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (01) : 303 - 312
[3] GEM-IL: A highly responsive fluorescent lactate indicator
Bekdash, Ramsey
Quejada, Jose R.
Ueno, Shunnosuke
Kawano, Fuun
Morikawa, Kumi
Klein, Alison D.
Matsumoto, Kenji
Lee, Tetz C.
Nakanishi, Koki
Chalan, Amy
Lee, Teresa M.
Liu, Rui
Homma, Shunichi
Lin, Chyuan-Sheng
Yelshanskaya, Maria, V
Sobolevsky, Alexander, I
Goda, Keisuke
Yazawa, Masayuki
[J]. CELL REPORTS METHODS, 2021, 1 (07):
[4] Berg J, 2009, NAT METHODS, V6, P161, DOI [10.1038/NMETH.1288, 10.1038/nmeth.1288]
[5] Genetically encoded fluorescent indicator for imaging NAD+/NADH ratio changes in different cellular compartments
Bilan, Dmitry S.
Matlashov, Mikhail E.
Gorokhovatsky, Andrey Yu.
Schultz, Carsten
Enikolopov, Grigori
Belousov, Vsevolod V.
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2014, 1840 (03): : 951 - 957
[6] Lactate and energy metabolism in male germ cells
Boussouar, F
Benahmed, M
[J]. TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (07) : 345 - 350
[7] The Science and Translation of Lactate Shuttle Theory
Brooks, George A.
[J]. CELL METABOLISM, 2018, 27 (04) : 757 - 785
[8] Elevated Lactate Levels in Patients With Poorly Regulated Type 1 Diabetes and Glycogenic Hepatopathy: A New Feature of Mauriac Syndrome
Brouwers, Martijn C. G. J.
Ham, Janneke C.
Wisse, Eddie
Misra, Shivani
Landewe, Sabine
Rosenthal, Miranda
Patel, Dipesh
Oliver, Nick
Bilo, Henk J. G.
Murphy, Elaine
[J]. DIABETES CARE, 2015, 38 (02) : E11 - E12
[9] Biosensor reveals multiple sources for mitochondrial NAD+
Cambronne, Xiaolu A.
Stewart, Melissa L.
Kim, DongHo
Jones-Brunette, Amber M.
Morgan, Rory K.
Farrens, David L.
Cohen, Michael S.
Goodman, Richard H.
[J]. SCIENCE, 2016, 352 (6292) : 1474 - 1477
[10] Cameron WD, 2016, NAT METHODS, V13, P352, DOI [10.1038/NMETH.3764, 10.1038/nmeth.3764]

← 1 2 3 4 5 6 7 →