Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure
Takaaki Furihata, Shingo Takada, Naoya Kakutani, Satoshi Maekawa, Masaya Tsuda, Junichi Matsumoto, Wataru Mizushima, Arata Fukushima, Takashi Yokota, Nobuyuki Enzan, Shouji Matsushima, Haruka Handa, Yoshizuki Fumoto, Junko Nio‐Kobayashi, Toshihiko Iwanaga, Shinya Tanaka, Hiroyuki Tsutsui, Hisataka Sabe, Shintaro Kinugawa
Abstract
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.