Pro- and Antioxidant Functions of the Peroxisome-Mitochondria Connection and Its Impact on Aging and Disease

Abstract

Peroxisomes and mitochondria are the main intracellular sources for reactive oxygen species. At the same time, both organelles are critical for the maintenance of a healthy redox balance in the cell. Consequently, failure in the function of both organelles is causally linked to oxidative stress and accelerated aging. However, it has become clear that peroxisomes and mitochondria are much more intimately connected both physiologically and structurally. Both organelles share common fission components to dynamically respond to environmental cues, and the autophagic turnover of both peroxisomes and mitochondria is decisive for cellular homeostasis. Moreover, peroxisomes can physically associate with mitochondria via specific protein complexes. Therefore, the structural and functional connection of both organelles is a critical and dynamic feature in the regulation of oxidative metabolism, whose dynamic nature will be revealed in the future. In this review, we will focus on fundamental aspects of the peroxisome-mitochondria interplay derived from simple models such as yeast and move onto discussing the impact of an impaired peroxisomal and mitochondrial homeostasis on ROS production, aging, and disease in humans.

Propofol protects human cardiac cells against chemical hypoxiainduced injury by regulating the JNK signaling pathways

“…Propofol reduces CoCl 2 -induced oxidative stress in AC16 and HCM cells. Mitochondria are considered the main source of ROS in cells (24). Therefore, the present study investigated the mechanism underlying the propofol-induced mitochondrial protection from oxidative stress.…”

Genome-wide epigenetic analyses in Japanese immigrant plantation workers with Parkinson’s Disease and exposure to organochlorines reveal possible involvement of glial genes and pathways involved in neurotoxicity

“…Both are equipped with their own ROS scavenging repertoire of enzymes and hence are key organelles in maintaining cellular ROS homeostasis. Peroxisomes contain several antioxidant systems, which are important for ROS homeostasis, e.g., the β-oxidation pathway, which directly produces H2O2, which is detoxi ed by catalase activity and is of central importance for redox balance of the organelle [80] [81]. When peroxisomes are either damaged by excessive ROS production these are marked by ubiquitination, which in mammalian cells is a common signal that triggers autophagy, and pexophagy.…”

“…When peroxisomes are either damaged by excessive ROS production these are marked by ubiquitination, which in mammalian cells is a common signal that triggers autophagy, and pexophagy. Thus, peroxisomal (together with mitochondrial) activity in maintaining the cellular redox state is important for cell survival and health [81] [82] [83].…”

Autophagy as a protective mechanism in oxidative stress

“…В клетках наряду с митохондриями пероксисомы являются основными потребителями O 2 , который используется ферментами для отщепления атомов водорода от некоторых органических субстратов с образованием перекиси водорода, в последующем фенолов, формальдегида, ýтанола и других соединений [77]. Выступая ýффективными продуцентами АКМ, пероксисомы также содержат большое количество ферментов их детоксикации (тиоредоксин 2, глутаредоксины 2 и 5, пероксиредоксины 3 и 5, глутатионпероксидазы и глутатионредуктаза, Cu,Zn-и Mn-супероксиддисмутазы), поýтому рассматриваются как один из главных регуляторов редокс-баланса в клетках [78]. Основными генераторами АКМ в пероксисомах выступают флавиновые оксидазы: полиаминоксидазы, оксидазы D-и L-аминокислот, ксантиноксидаза, уратоксидаза, которые восстанавливают молекулярный кислород до Н 2 О 2 [79].…”

“…В отличие от О − • 2 , не имеющие заряда молекулы NO· и Н 2 О 2 достаточно легко диффундируют в цитоплазму. Посредством продукции АКМ пероксисомы взаимодействуют с митохондриями и совместно участвуют в регуляции широкого спектра редокс-зависимых процессов в клетках [78].…”