当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production.

Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production.

Abstract：

:Although many types of ancient bacteria and archea rely on hydrogen sulfide (H(2)S) for their energy production, eukaryotes generate ATP in an oxygen-dependent fashion. We hypothesize that endogenous H(2)S remains a regulator of energy production in mammalian cells under stress conditions, which enables the body to cope with energy demand when oxygen supply is insufficient. Cystathionine γ-lyase (CSE) is a major H(2)S-producing enzyme in the cardiovascular system that uses cysteine as the main substrate. Here we show that CSE is localized only in the cytosol, not in mitochondria, of vascular smooth-muscle cells (SMCs) under resting conditions, revealed by Western blot analysis and confocal microscopy of SMCs transfected with GFP-tagged CSE plasmid. After SMCs were exposed to A23187, thapsigargin, or tunicamycin, intracellular calcium level was increased, and CSE translocated from the cytosol to mitochondria. CSE was coimmunoprecipitated with translocase of the outer membrane 20 (Tom20) in mitochondrial membrane. Tom20 siRNA significantly inhibited mitochondrial translocation of CSE and mitochondrial H(2)S production. The cysteine level inside mitochondria is approximately three times that in the cytosol. Translocation of CSE to mitochondria metabolized cysteine, produced H(2)S inside mitochondria, and increased ATP production. Inhibition of CSE activity reversed A23187-stimulated mitochondrial ATP production. H(2)S improved mitochondrial ATP production in SMCs with hypoxia, which alone decreased ATP production. These results suggest that translocation of CSE to mitochondria on specific stress stimulations is a unique mechanism to promote H(2)S production inside mitochondria, which subsequently sustains mitochondrial ATP production under hypoxic conditions.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Fu M,Zhang W,Wu L,Yang G,Li H,Wang R

doi

10.1073/pnas.1115634109

subject

Has Abstract

pub_date

2012-02-21 00:00:00

pages

2943-8

issue

eissn

0027-8424

issn

1091-6490

pii

1115634109

journal_volume

109

pub_type

杂志文章

在线工具

Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production.