Mitochondrial Homeostasis and Cellular Senescence

Abstract

Cellular senescence refers to a stress response aiming to preserve cellular and, therefore, organismal homeostasis. Importantly, deregulation of mitochondrial homeostatic mechanisms, manifested as impaired mitochondrial biogenesis, metabolism and dynamics, has emerged as a hallmark of cellular senescence. On the other hand, impaired mitostasis has been suggested to induce cellular senescence. This review aims to provide an overview of homeostatic mechanisms operating within mitochondria and a comprehensive insight into the interplay between cellular senescence and mitochondrial dysfunction.

Keywords: cellular senescence; mitochondria; mitochondrial dynamics; mitostasis.

Figure 1

Maintaining homeostasis is the cornerstone for cells’ normal function, ensuring organismal physiology. Intriguingly, cells are constantly exposed to intrinsic and extrinsic stressors that jeopardize cellular integrity and activate a variety of response modules, through complex and highly sophisticated biochemical networks. Depending on the intensity and duration of the stressor, cellular response mechanisms either manage to neutralize the adverse effects of stress, thus achieving complete recovery and survival, or lead to death in case of non-repairable damage. Between these two opposite outcomes reminiscent of the swinging of a pendulum, cellular senescence enters the scene.

Figure 2

Senescent cell with enlarged mitochondria with disturbed morphology of cristae distributed mostly at their periphery, forming circular constructions, or partially lost. N: nucleus. Scale bar: 1 μm.

Figure 3

Elongated mitochondria in the cytoplasm of a senescent cell with partial loss of cristae. N: nucleus. Scale bar: 500 nm.

Figure 4

Branched mitochondrion in the cytoplasm of a senescent cell with partial loss of cristae. Scale bar: 500 nm.