Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence.

Author: Park JT1, Lee YS2, Cho KA3, Park SC4
Author Information:
1Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Republic of Korea.
2Well Aging Research Center, DGIST, Daegu, Republic of Korea; Department of New Biology, DGIST, Daegu, Republic of Korea.
3Department of Biochemistry, Chonnam National University Medical School, Gwangju, Republic of Korea.
4Well Aging Research Center, DGIST, Daegu, Republic of Korea; The Future Life & Society Research Center, Chonnam National University, Gwangju, Republic of Korea. Electronic address:
Conference/Journal: Ageing Res Rev.
Date published: 2018 Aug 21
Other: Pages: S1568-1637(18)30168-5 , Special Notes: doi: 10.1016/j.arr.2018.08.003. [Epub ahead of print] , Word Count: 204

Mitochondria and lysosomes undergo the most marked senescence-related alterations among all cellular organelles. Whereas mitochondria undergo gradual structural changes associated with reduced function, lysosomes exhibit progressively deteriorated function along with the accumulation of lipofuscins. Lysosomal dysfunction induces the deterioration of mitochondrial turnover, resulting in the generation of more reactive oxygen species (ROS), with the increased ROS levels in turn targeting lysosomes. This vicious feedback loop between lysosomes and mitochondria thus aggravates senescence phenotypes. Based on findings that lysosomal activity is diminished in senescent cells and that the resultant oxidative stress correlates with mitochondrial damage, the existence of a lysosomal-mitochondrial axis with a functional role in senescence has been proposed. In this review, we interrogate the interplay between lysosomes and mitochondria during senescence and propose the lysosomal-mitochondrial axis to serve a potential function as an inducer of senescence alleviation. Thus, learning how to control the lysosomal-mitochondrial axis should represent an important research directive for developing therapeutics toward ageing-related disease as well as the aging process itself. Further research focusing on the lysosomal-mitochondrial axis will add to our knowledge regarding aging and age-related pathologies, as well as provide new strategies for anti-aging intervention.

KEYWORDS: aging; autophagy; lysosomal-mitochondrial axis; lysosome; mitochondria; senescence alleviation

PMID: 30142381 DOI: 10.1016/j.arr.2018.08.003