TY - JOUR
T1 - Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure
AU - Furihata, Takaaki
AU - Takada, Shingo
AU - Kakutani, Naoya
AU - Maekawa, Satoshi
AU - Tsuda, Masaya
AU - Matsumoto, Junichi
AU - Mizushima, Wataru
AU - Fukushima, Arata
AU - Yokota, Takashi
AU - Enzan, Nobuyuki
AU - Matsushima, Shouji
AU - Handa, Haruka
AU - Fumoto, Yoshizuki
AU - Nio-Kobayashi, Junko
AU - Iwanaga, Toshihiko
AU - Tanaka, Shinya
AU - Tsutsui, Hiroyuki
AU - Sabe, Hisataka
AU - Kinugawa, Shintaro
N1 - Funding Information:
The authors thank Mami Sato of the Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, for the transmission electron microscopy analysis, and Yuki Kimura, Noriko Ikeda, and Miwako Yamane for their technical assistance. This work was supported in part by Grants-In-Aid for Scientific Research (JP17K15979 [to T.F.], JP17K10137 [to A.F.], JP17H04758 [to S.T.], 18K08022 [to T.Y.], 18H03187 [to S.K.], 26350879 [to S.K.], and 15H04815 [to H.T.]) from the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Heart failure (HF) occurs frequently among older individuals, and dysfunction of cardiac mitochondria is often observed. We here show the cardiac-specific downregulation of a certain mitochondrial component during the chronological aging of mice, which is detrimental to the heart. MitoNEET is a mitochondrial outer membrane protein, encoded by CDGSH iron sulfur domain 1 (CISD1). Expression of mitoNEET was specifically downregulated in the heart and kidney of chronologically aged mice. Mice with a constitutive cardiac-specific deletion of CISD1 on the C57BL/6J background showed cardiac dysfunction only after 12 months of age and developed HF after 16 months; whereas irregular morphology and higher levels of reactive oxygen species in their cardiac mitochondria were observed at earlier time points. Our results suggest a possible mechanism by which cardiac mitochondria may gradually lose their integrity during natural aging, and shed light on an uncharted molecular basis closely related to age-associated HF.
AB - Heart failure (HF) occurs frequently among older individuals, and dysfunction of cardiac mitochondria is often observed. We here show the cardiac-specific downregulation of a certain mitochondrial component during the chronological aging of mice, which is detrimental to the heart. MitoNEET is a mitochondrial outer membrane protein, encoded by CDGSH iron sulfur domain 1 (CISD1). Expression of mitoNEET was specifically downregulated in the heart and kidney of chronologically aged mice. Mice with a constitutive cardiac-specific deletion of CISD1 on the C57BL/6J background showed cardiac dysfunction only after 12 months of age and developed HF after 16 months; whereas irregular morphology and higher levels of reactive oxygen species in their cardiac mitochondria were observed at earlier time points. Our results suggest a possible mechanism by which cardiac mitochondria may gradually lose their integrity during natural aging, and shed light on an uncharted molecular basis closely related to age-associated HF.
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U2 - 10.1038/s42003-021-01675-4
DO - 10.1038/s42003-021-01675-4
M3 - Article
C2 - 33514783
AN - SCOPUS:85099981954
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 138
ER -