**1. Introduction**

Mitochondria are intracellular organelles present in eukaryotic cells that evolutionarily originated from symbiotic resident proteobacteria [1]. These organelles are involved in many cellular functions, such as oxidative phosphorylation, the regulation of cell proliferation, differentiation, and death. Their different roles in several cellular processes are largely dependent on ATP and reactive oxygen species (ROS) production, both generated during oxidative phosphorylation [2]. Indeed, targeting mitochondrial metabolism with molecules able to specifically disrupt mitochondrial fitness and trigger cell death has become a promising strategy against several diseases [3].

Importantly, mitochondria are physically interconnected with other subcellular organelles, such as endoplasmic reticulum (ER), lipid droplets, Golgi apparatus, lysosomes, melanosomes, and peroxisomes [4]. Indeed, mitochondria–organelle contact sites represent real signaling hubs that are involved in multiple cellular functions, such as lipid trafficking, mitochondrial dynamics, calcium (Ca 2+ ) flow, and ER stress, such that the contacts not only result in physical but also functional links that finely tune multiple signaling pathways.

Moreover, the capability to establish these interactions with other intracellular organelles is strongly dependent on mitochondria's high attitude to fuse and divide, leading to modification of the intracellular mitochondrial network [5].

In addition, ROS figure as byproducts of oxygen consumption and cellular metabolism, and 45% of their total amount is related to mitochondria, specifically to Complex I and

**Citation:** Brillo, V.; Chieregato, L.; Leanza, L.; Muccioli, S.; Costa, R. Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview. *Life* **2021**, *11*, 332. https://doi.org/ 10.3390/life11040332

Academic Editors: Giorgio Lenaz and Salvatore Nesci

Received: 2 March 2021 Accepted: 7 April 2021 Published: 10 April 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Complex III leakage of electrons, which is involved in superoxide (O<sup>2</sup> <sup>−</sup>) and hydrogen peroxide (H2O2) production [6]. While ROS production was at first believed to be only detrimental for the cell in physiological conditions, in the last two decades, it has been considered that its presence in a sublethal concentration could act as a secondary messenger that specifically modulates distinct cellular pathways [7] and mitochondrial dynamics and morphology [8]. As a consequence, ROS homeostasis is strictly regulated by enzymatic and nonenzymatic mechanisms, with the aim of maintaining balance among ROS production and scavenging [9]. Once this critical equilibrium is impaired, ROS overload is one of the main players in the onset of a plethora of different diseases, including cancer [6], where it exerts a dual regulation, influencing cell survival and oxidative stress, leading to cell death, as well as mediating redox signaling events beneficial for the progression of the disease [9].

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In this review, we describe the known signaling pathways mediated by mitochondrial structure rearrangements or by mitochondrial ROS release, focusing also on possible therapeutic targets against disease formation.
